Laboratory of Molecular Therapy

Design and development of novel anti-cancer agents, in particular vitamin E analogues, that are efficient and selective for malignant cells

Group leader: prof. Ing. Jiří Neužil, CSc.

Jiri Neuzil is the Head of the Laboratory of Molecular Therapy (LMT). In collaboration with his Australian group (Mitochondria, Apoptosis and Cancer Research Group, Griffith University, Southport, Qld, Australia), the laboratory focuses on the design and development of novel anti-cancer agents, in particular vitamin E analogues, that are efficient and selective for malignant cells. The researchers are especially interested in the molecular mechanism of apoptosis caused by such agents, which includes pathways of mitochondrial destabilisation. They have defined and characterized the group of ‘mitocans’, small molecules relaying their anti-cancer activity via mitochondria. These agents are particularly intriguing from  the translational point of view, since it is now clear that tumours are extremely heterogeneous in their mutations, even within different regions of the same tumour. Therefore, mitochondria may present an invariant target that can be utilized for cancer therapy.

A particular focus of the group is on mitocans from the group of vitamin E analogues, represented by the redox-silent compound α-tocopheryl succinate (α-TOS). This agent exerts high apoptogenic activity towards a variety of cancer cell lines while being non-toxic to normal cells. This in vitro pro-apoptotic activity is matched by its anti-cancer activity in mouse models of tumours, which the group has shown for colorectal, breast and mesothelioma tumours. This finding endows α-TOS with substantial translational spin and/or makes it a lead compound for the design of more efficient agents.

In the attempt to characterize the pathway(s) regulating apoptotic signalling in cancer cells triggered by α-TOS, the researchers discovered a new target of anti-cancer drugs, the mitochondrial complex II (CII). Interestingly, they found that α-TOS (and similar compounds) interacts with the proximal and distal ubiquinone (UbQ)-binding site of CII, thereby replacing UbQ in CII. CII, by means of its succinate dehydrogenase (SDH) activity, converts succinate to fumarate as a component of the tricarboxylic acid (TCA) cycle. Electrons released from this reaction are normally intercepted by UbQ and donated to CIII of the electron transport chain (ETC), part of oxidative phosphorylation. In case UbQ is replaced by α-TOS or similar compounds, the electrons recombine with molecular oxygen and cause generation of superoxide, triggering the apoptosis signalling cascade. Since genes coding for the subunit of CII mutate only exceptionally, the complex presents a very intriguing target for anti-cancer drugs.

In the attempt to increase the apoptogenic activity of α-TOS, the agent was modified by tagging with the cationic triphenylphosphonium (TPP) group, which causes the accumulation of the agent (mitochondrially targeted vitamin E succinate, MitoVES) at the interface of the mitochondrial inner membrane and the mitochondrial matrix, enhancing the apoptogenic activity of the parental compound by 1–2 orders of magnitude. Importantly, this increase in toxicity towards cancer cells did not compromise the selectivity of the agent for malignant cells. The approach of the group to cancer therapy by tagging anti-cancer agents with lipophilic cations epitomised by TPP presents a novel paradigm of efficient cancer therapy. The group is further pursuing this line of research to synthesize novel, more efficient anti-cancer agents targeting mitochondria. In particular, they plan to initiate translational research, whereby delivering their novel agents to the clinic. If successful, this may change the landscape of current and future cancer therapeutic modalities potentially leading to efficient cancer treatment.

Anděra Ladislav, RNDr., CSc.
Bálintová Soňa, Mgr.
Benešová Simona
Boukalová Štěpána, Mgr., Ph.D.
Brisudová Petra, Mgr.
Dubišová Mária, Mgr.
Dvořáková Šárka, RNDr., Ph.D.
Endaya Berwini Beduya
Hrysiuk Mariia
Jarošová Kateřina
Kořínková Klára, Mgr.
Kovářová Jaromíra, Mgr., Ph.D.
Le Thi Dan Diem
Lopes Oliveira Gabriela
Nahácka Zuzana, Mgr., Ph.D.
Nahácka Zuzana, Mgr., Ph.D.
Neužil Jiří, prof. Ing., CSc.
Novák Jaromír, Mgr.
Nováková Anna, Mgr.
Prost Salomé
Sovilj Dana
Štemberková - Hubáčková Soňa, RNDr., Ph.D.
Vacurová Eliška, Mgr.
Zobalová Renata, Mgr., Ph.D.


  • Boukalova, S., Ezrova, Z., & Neuzil, J. (2021). "Mechanisms of resistance to mitochondria-targeted therapy in pancreatic cancer." Oncotarget, 12(16), 1627-1628.

  • Ezrova, Z., Nahacka, Z., Stursa, J., Werner, L., Vlcak, E., Kralova Viziova, P., Berridge, M. V., Sedlacek, R., Zobalova, R., Rohlena, J., Boukalova, S., Neuzil, J. (2021). "SMAD4 loss limits the vulnerability of pancreatic cancer cells to complex I inhibition via promotion of mitophagy." Oncogene.

  • Gaetani, S., Galzignati, L., Marcati, M., Durazzi, P., Cianella, A., Mocheggiani, V., Monaco, F., Bracci, M., Neuzil, J., Tomasetti, M., Amati, M., & Santarelli, L. (2021)."Mitochondrial function as related to psychological distress in health care professionals." Psychosom Med.

  • Hadrava Vanova, K., Pang, Y., Krobova, L., Kraus, M., Nahacka, Z., Boukalova, S., Pack, S. D., Zobalova, R., Zhu, J., Huynh, T. T., Jochmanova, I., Uher, O., Hubackova, S., Dvorakova, S., Garrett, T. J., Ghayee, H. K., Wu, X., Schuster, B., Knapp, P. E., Frysak, Z., Hartmann, I., Nilubol, N., Cerny, J., Taieb, D., Rohlena, J., Neuzil, J., Yang, C., & Pacak, K. (2021). Germline SUCLG2 Variants in Patients with Pheochromocytoma and Paraganglioma. J Natl Cancer Inst.

  • Hadrava Vanova, K., Yang, C., Meuter, L., Neuzil, J., & Pacak, K. (2021). Reactive Oxygen Species: A Promising Therapeutic Target for SDHx-Mutated Pheochromocytoma and Paraganglioma. Cancers (Basel), 13(15).

  • Klener, P., Sovilj, D., Renesova, N., & Andera, L. (2021)." BH3 Mimetics in Hematologic Malignancies." Int J Mol Sci, 22(18). (ASEP)

  • Levoux, J., Prola, A., Lafuste, P., Gervais, M., Chevallier, N., Koumaiha, Z., Kefi, K., Braud, L., Schmitt, A., Yacia, A., Schirmann, A., Hersant, B., Sid-Ahmed, M., Ben Larbi, S., Komrskova, K., Rohlena, J., Relaix, F., Neuzil, J., & Rodriguez, A. M. (2021b, Mar 2). Platelets facilitate the wound-healing capability of mesenchymal stem cells by mitochondrial transfer and metabolic reprogramming. Cell Metabolism, 33(3), 688-690.

  • Matlac, D. M., Hadrava Vanova, K., Bechmann, N., Richter, S., Folberth, J., Ghayee, H. K., Ge, G. B., Abunimer, L., Wesley, R., Aherrahrou, R., Dona, M., Martinez-Montes, A. M., Calsina, B., Merino, M. J., Schwaninger, M., Deen, P. M. T., Zhuang, Z., Neuzil, J., Pacak, K., Lehnert, H., & Fliedner, S. M. J. (2021). "Succinate Mediates Tumorigenic Effects via Succinate Receptor 1: Potential for New Targeted Treatment Strategies in Succinate Dehydrogenase Deficient Paragangliomas." Front Endocrinol (Lausanne), 12, 589451.

  • Nahacka, Z., Zobalova, R., Dubisova, M., Rohlena, J., Neuzil, J. (2021)."Miro proteins connect mitochondrial function and intercellular transport." Crit Rev Biochem Mol Biol, 1-25.

  • Sandoval-Acuna, C., Torrealba, N., Tomkova, V., Jadhav, S. B., Blazkova, K., Merta, L., Lettlova, S., Adamcova, M. K., Rosel, D., Brabek, J., Neuzil, J., Stursa, J., Werner, L., Truksa, J. (2021). "Targeting mitochondrial iron metabolism suppresses tumor growth and metastasis by inducing mitochondrial dysfunction and mitophagy." Cancer Res.

  • Simoes, R. F., Pino, R., Moreira-Soares, M., Kovarova, J., Neuzil, J., Travasso, R., Oliveira, P. J., Cunha-Oliveira, T., & Pereira, F. B. (2021). "Quantitative analysis of neuronal mitochondrial movement reveals patterns resulting from neurotoxicity of rotenone and 6-hydroxydopamine." FASEB J, 35(12), e22024.

  • Valdinocci, D., Kovarova, J., Neuzil, J., Pountney, D. L. (2021). "Alpha-Synuclein Aggregates Associated with Mitochondria in Tunnelling Nanotubes." Neurotox Res, 39(2), 429-443. (ASEP)

  • Vidimce, J., Pillay, J., Shrestha, N., Dong, L. F., Neuzil, J., Wagner, K. H., Holland, O. J., Bulmer, A. C. (2021). "Mitochondrial Function, Fatty Acid Metabolism, and Body Composition in the Hyperbilirubinemic Gunn Rat." Front Pharmacol, 12, 586715.


  • Boukalova, S., S. Hubackova, M. Milosevic, Z. Ezrova, J. Neuzil and J. Rohlena (2020). "Dihydroorotate dehydrogenase in oxidative phosphorylation and cancer." Biochim Biophys Acta Mol Basis Dis 1866(6): 165759.
  • Dong, L., Gopalan, V., Holland, O., & Neuzil, J. (2020). "Mitocans Revisited: Mitochondrial Targeting as Efficient Anti-Cancer Therapy." Int J Mol Sci, 21(21).
  • Gaetani, S., F. Monaco, F. Alessandrini, A. Tagliabracci, A. Sabbatini, M. Bracci, M. Valentino, J. Neuzil, M. Amati, L. Santarelli and M. Tomasetti (2020). "Mechanism of miR-222 and miR-126 regulation and its role in asbestos-induced malignancy." Int J Biochem Cell Biol: 105700.

  • Grasso, C., Eccles, D. A., Boukalova, S., Fabre, M. S., Dawson, R. H., Neuzil, J., Herst, P. M., & Berridge, M. V. (2020). Mitochondrial DNA Affects the Expression of Nuclear Genes Involved in Immune and Stress Responses in a Breast Cancer Model. Front Physiol, 11, 543962.
  • Hadrava Vanova, K., Kraus, M., Neuzil, J., & Rohlena, J. (2020). "Mitochondrial complex II and reactive oxygen species in disease and therapy." Redox Rep, 25(1), 26-32.

  • Henrichs, V., Grycova, L., Barinka, C., Nahacka, Z., Neuzil, J., Diez, S., Rohlena, J., Braun, M., & Lansky, Z. (2020). "Mitochondria-adaptor TRAK1 promotes kinesin-1 driven transport in crowded environments." Nature Communications, 11(1), 3123.
  • Hubackova, S., E. Davidova, S. Boukalova, J. Kovarova, M. Bajzikova, A. Coelho, M. G. Terp, H. J. Ditzel, J. Rohlena and J. Neuzil (2020). "Replication and ribosomal stress induced by targeting pyrimidine synthesis and cellular checkpoints suppress p53-deficient tumors." Cell Death Dis 11(2): 110.

  • Liu, Y., Pang, Y., Zhu, B., Uher, O., Caisova, V., Huynh, T. T., Taieb, D., Hadrava Vanova, K., Ghayee, H. K., Neuzil, J., Levine, M., Yang, C., & Pacak, K. (2020). "Therapeutic Targeting of SDHB-Mutated Pheochromocytoma/Paraganglioma with Pharmacologic Ascorbic Acid." Clin Cancer Res, 26(14), 3868-3880.
  • Raninga, P. V., Lee, A., Sinha, D., Dong, L. F., Datta, K. K., Lu, X., Kalita-de Croft, P., Dutt, M., Hill, M., Pouliot, N., Gowda, H., Kalimutho, M., Neuzil, J., & Khanna, K. K. (2020). "Marizomib suppresses triple-negative breast cancer via proteasome and oxidative phosphorylation inhibition." Theranostics, 10(12), 5259-5275.
  • Valdinocci, D., Kovarova, J., Neuzil, J., & Pountney, D. L. (2020). "Alpha-Synuclein Aggregates Associated with Mitochondria in Tunnelling Nanotubes." Neurotox Res.


  • Bajzikova, M., J. Kovarova, A. R. Coelho, S. Boukalova, S. Oh, K. Rohlenova, D. Svec, S. Hubackova, B. Endaya, K. Judasova, A. Bezawork-Geleta, K. Kluckova, L. Chatre, R. Zobalova, A. Novakova, K. Vanova, Z. Ezrova, G. J. Maghzal, S. M. Novais, M. Olsinova, L. Krobova, Y. J. An, E. Davidova, Z. Nahacka, M. Sobol, T. Cunha-Oliveira, C. Sandoval-Acuna, H. Strnad, T. C. Zhang, T. Huynh, T. L. Serafim, P. Hozak, V. A. Sardao, W. J. H. Koopman, M. Ricchetti, P. J. Oliveira, F. Kolar, M. Kubista, J. Truksa, K. Dvorakova-Hortova, K. Pacak, R. Gurlich, R. Stocker, Y. Q. Zhou, M. V. Berridge, S. Park, L. F. Dong, J. Rohlena and J. Neuzil (2019). "Reactivation of Dihydroorotate Dehydrogenase-Driven Pyrimidine Biosynthesis Restores Tumor Growth of Respiration-Deficient Cancer Cells." Cell Metabolism 29(2): 399-+.

  • Hubackova, S., M. Pribyl, L. Kyjacova, A. Moudra, R. Dzijak, B. Salovska, H. Strnad, V. Tambor, T. Imrichova, J. Svec, P. Vodicka, R. Vaclavikova, L. Rob, J. Bartek and Z. Hodny (2019). "Interferon-regulated suprabasin is essential for stress-induced stem-like cell conversion and therapy resistance of human malignancies." Mol Oncol 13(7): 1467-1489.

  • Jha, A., K. de Luna, C. A. Balili, C. Millo, C. A. Paraiso, A. Ling, M. K. Gonzales, B. Viana, R. Alrezk, K. T. Adams, I. Tena, A. Chen, J. Neuzil, M. Raygada, E. Kebebew, D. Taieb, M. S. O'Dorisio, T. O'Dorisio, A. C. Civelek, C. A. Stratakis, L. Mercado-Asis and K. Pacak (2019). "Clinical, Diagnostic, and Treatment Characteristics of SDHA-Related Metastatic Pheochromocytoma and Paraganglioma." Front Oncol 9: 53.

  • Monaco, F., S. Gaetani, F. Alessandrini, A. Tagliabracci, M. Bracci, M. Valentino, J. Neuzil, M. Amati, M. Bovenzi, M. Tomasetti and L. Santarelli (2019). "Exosomal transfer of miR-126 promotes the anti-tumour response in malignant mesothelioma: Role of miR-126 in cancer-stroma communication." Cancer Lett 463: 27-36.

  • Prukova, D., L. Andera, Z. Nahacka, J. Karolova, M. Svaton, M. Klanova, O. Havranek, J. Soukup, K. Svobodova, Z. Zemanova, D. Tuskova, E. Pokorna, K. Helman, K. Forsterova, M. Pacheco-Blanco, P. Vockova, A. Berkova, E. Fronkova, M. Trneny and P. Klener (2019). "Cotargeting of BCL2 with Venetoclax and MCL1 with S63845 Is Synthetically Lethal In Vivo in Relapsed Mantle Cell Lymphoma." Clin Cancer Res 25(14): 4455-4465.

  • Santarelli, L., S. Gaetani, F. Monaco, M. Bracci, M. Valentino, M. Amati, C. Rubini, A. Sabbatini, E. Pasquini, N. Zanotta, M. Comar, J. Neuzil, M. Tomasetti and M. Bovenzi (2019). "Four-miRNA Signature to Identify Asbestos-Related Lung Malignancies." Cancer Epidemiol Biomarkers Prev 28(1): 119-126.

  • Stetka, J., P. Vyhlidalova, L. Lanikova, P. Koralkova, J. Gursky, A. Hlusi, P. Flodr, S. Hubackova, J. Bartek, Z. Hodny and V. Divoky (2019). "Addiction to DUSP1 protects JAK2V617F-driven polycythemia vera progenitors against inflammatory stress and DNA damage, allowing chronic proliferation." Oncogene 38(28): 5627-5642.

  • Tomasetti, M., S. Gaetani, F. Monaco, J. Neuzil and L. Santarelli (2019). "Epigenetic Regulation of miRNA Expression in Malignant Mesothelioma: miRNAs as Biomarkers of Early Diagnosis and Therapy." Front Oncol 9: 1293.

  • Valdinocci, D., R. F. Simoes, J. Kovarova, T. Cunha-Oliveira, J. Neuzil and D. L. Pountney (2019). "Intracellular and Intercellular Mitochondrial Dynamics in Parkinson's Disease." Front Neurosci 13: 930.


  • Berridge, M. V., C. Crasso and J. Neuzil (2018). "Mitochondrial Genome Transfer to Tumor Cells Breaks The Rules and Establishes a New Precedent in Cancer Biology." Mol Cell Oncol 5(5): e1023929.

  • Bezawork-Geleta, A., H. Wen, L. F. Dong, B. Yan, J. Vider, S. Boukalova, L. Krobova, K. Vanova, R. Zobalova, M. Sobol, P. Hozak, S. M. Novais, V. Caisova, P. Abaffy, R. Naraine, Y. Pang, T. Zaw, P. Zhang, R. Sindelka, M. Kubista, S. Zuryn, M. P. Molloy, M. V. Berridge, K. Pacak, J. Rohlena, S. Park and J. Neuzil (2018). "Alternative assembly of respiratory complex II connects energy stress to metabolic checkpoints." Nature Communications 9.

  • Cuyas, E., S. Verdura, L. Llorach-Pares, S. Fernandez-Arroyo, F. Luciano-Mateo, N. Cabre, J. Stursa, L. Werner, B. Martin-Castillo, B. Viollet, J. Neuzil, J. Joven, A. Nonell-Canals, M. Sanchez-Martinez and J. A. Menendez (2018). "Metformin directly targets the H3K27me3 demethylase KDM6A/UTX." Aging Cell 17(4): e12772.

  • Cuyas, E., S. Fernandez-Arroyo, S. Verdura, R. A. Garcia, J. Stursa, L. Werner, E. Blanco-Gonzalez, M. Montes-Bayon, J. Joven, B. Viollet, J. Neuzil and J. A. Menendez (2018). "Metformin regulates global DNA methylation via mitochondrial one-carbon metabolism." Oncogene 37(7): 963-970.

  • Hubackova, S., S. M. Novais, E. Davidova, J. Neuzil and J. Rohlena (2018). "Mitochondria-Driven Elimination of Cancer and Senescent Cells." Biol Chem.

  • Hubackova, S., E. Davidova, K. Rohlenova, J. Stursa, L. Werner, L. Andera, L. Dong, M. G. Terp, Z. Hodny, H. J. Ditzel, J. Rohlena and J. Neuzil (2018). "Selective elimination of senescent cells by mitochondrial targeting is regulated by ANT2." Cell Death Differ.

  • Nahacka, Z., J. Svadlenka, M. Peterka, M. Ksandrova, S. Benesova, J. Neuzil and L. Andera (2018). "TRAIL induces apoptosis but not necroptosis in colorectal and pancreatic cancer cells preferentially via the TRAIL-R2/DR5 receptor." Biochim Biophys Acta Mol Cell Res 1865(3): 522-531.

  • Pan, J., Y. Lee, G. Cheng, J. Zielonka, Q. Zhang, M. Bajzikova, D. Xiong, S. W. Tsaih, M. Hardy, M. Flister, C. M. Olsen, Y. Wang, O. Vang, J. Neuzil, C. R. Myers, B. Kalyanaraman and M. You (2018). "Mitochondria-Targeted Honokiol Confers a Striking Inhibitory Effect on Lung Cancer via Inhibiting Complex I Activity." iScience 3: 192-207.

  • Tomasetti, M., M. Re, F. Monaco, S. Gaetani, C. Rubini, A. Bertini, E. Pasquini, C. Bersaglieri, M. Bracci, S. Staffolani, M. Colomba, A. Gregorini, M. Valentino, A. Tagliabracci, M. Bovenzi, J. Neuzil, M. Amati and L. Santarelli (2018). "MiR-126 in intestinal-type sinonasal adenocarcinomas: exosomal transfer of MiR-126 promotes anti-tumour responses." BMC Cancer 18(1): 896.


  • Berridge, M. V. and J. Neuzil (2017). "The mobility of mitochondria: Intercellular trafficking in health and disease." Clin Exp Pharmacol Physiol 44 Suppl 1: 15-20.

  • Bezawork-Geleta, A., J. Rohlena, L. Dong, K. Pacak and J. Neuzil (2017). "Mitochondrial Complex II: At the Crossroads." Trends Biochem Sci 42(4): 312-325.

  • Blecha, J., S. M. Novais, K. Rohlenova, E. Novotna, S. Lettlova, S. Schmitt, H. Zischka, J. Neuzil and J. Rohlena (2017). "Antioxidant defense in quiescent cells determines selectivity of electron transport chain inhibition-induced cell death." Free Radic Biol Med 112: 253-266.

  • Dong, L. F., J. Kovarova, M. Bajzikova, A. Bezawork-Geleta, D. Svec, B. Endaya, K. Sachaphibulkij, A. R. Coelho, N. Sebkova, A. Ruzickova, A. S. Tan, K. Kluckova, K. Judasova, K. Zamecnikova, Z. Rychtarcikova, V. Gopalan, L. Andera, M. Sobol, B. Yan, B. Pattnaik, N. Bhatraju, J. Truksa, P. Stopka, P. Hozak, A. K. Lam, R. Sedlacek, P. J. Oliveira, M. Kubista, A. Agrawal, K. Dvorakova-Hortova, J. Rohlena, M. V. Berridge and J. Neuzil (2017). "Horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondrial DNA-deficient cancer cells." Elife 6.

  • Grimolizzi, F., F. Monaco, F. Leoni, M. Bracci, S. Staffolani, C. Bersaglieri, S. Gaetani, M. Valentino, M. Amati, C. Rubini, F. Saccucci, J. Neuzil, M. Tomasetti and L. Santarelli (2017). "Exosomal miR-126 as a circulating biomarker in non-small-cell lung cancer regulating cancer progression." Sci Rep 7(1): 15277.

  • Rohlenova, K., K. Sachaphibulkij, J. Stursa, A. Bezawork-Geleta, J. Blecha, B. Endaya, L. Werner, J. Cerny, R. Zobalova, J. Goodwin, T. Spacek, E. Alizadeh Pesdar, B. Yan, M. N. Nguyen, M. Vondrusova, M. Sobol, P. Jezek, P. Hozak, J. Truksa, J. Rohlena, L. F. Dong and J. Neuzil (2017). "Selective Disruption of Respiratory Supercomplexes as a New Strategy to Suppress Her2(high) Breast Cancer." Antioxid Redox Signal 26(2): 84-103.

  • Rychtarcikova, Z., S. Lettlova, V. Tomkova, V. Korenkova, L. Langerova, E. Simonova, P. Zjablovskaja, M. Alberich-Jorda, J. Neuzil and J. Truksa (2017). "Tumor-initiating cells of breast and prostate origin show alterations in the expression of genes related to iron metabolism." Oncotarget 8(4): 6376-6398.

  • Tomasetti, M., W. Lee, L. Santarelli and J. Neuzil (2017). "Exosome-derived microRNAs in cancer metabolism: possible implications in cancer diagnostics and therapy." Exp Mol Med 49(1): e285.

  • Tomasetti, M., M. Amati, J. Neuzil and L. Santarelli (2017). "Circulating epigenetic biomarkers in lung malignancies: From early diagnosis to therapy." Lung Cancer 107: 65-72.


  • Berridge, M. V., M. J. McConnell, C. Grasso, M. Bajzikova, J. Kovarova and J. Neuzil (2016). "Horizontal transfer of mitochondria between mammalian cells: beyond co-culture approaches." Curr Opin Genet Dev 38: 75-82.

  • Bezawork-Geleta, A., L. Dong, J. Rohlena and J. Neuzil (2016). "The Assembly Factor SDHAF2 Is Dispensable for Flavination of the Catalytic Subunit of Mitochondrial Complex II in Breast Cancer Cells." J Biol Chem 291(41): 21414-21420.

  • Boukalova, S., J. Stursa, L. Werner, Z. Ezrova, J. Cerny, A. Bezawork-Geleta, A. Pecinova, L. Dong, Z. Drahota and J. Neuzil (2016). "Mitochondrial Targeting of Metformin Enhances Its Activity against Pancreatic Cancer." Mol Cancer Ther 15(12): 2875-2886.

  • Endaya, B., B. Cavanagh, F. Alowaidi, T. Walker, N. de Pennington, J. M. Ng, P. Y. Lam, A. Mackay-Sim, J. Neuzil and A. C. Meedeniya (2016). "Isolating dividing neural and brain tumour cells for gene expression profiling." J Neurosci Methods 257: 121-133.

  • Endaya, B. B., P. Y. Lam, A. C. Meedeniya and J. Neuzil (2016). "Transcriptional profiling of dividing tumor cells detects intratumor heterogeneity linked to cell proliferation in a brain tumor model." Mol Oncol 10(1): 126-137.

  • Moudra, A., S. Hubackova, V. Machalova, M. Vancurova, J. Bartek, M. Reinis, Z. Hodny and A. Jonasova (2016). "Dynamic alterations of bone marrow cytokine landscape of myelodysplastic syndromes patients treated with 5-azacytidine." Oncoimmunology 5(10): e1183860.

  • Rohlenova, K., J. Neuzil and J. Rohlena (2016). "The role of Her2 and other oncogenes of the PI3K/AKT pathway in mitochondria." Biol Chem 397(7): 607-615.

  • Tomasetti, M., F. Monaco, N. Manzella, J. Rohlena, K. Rohlenova, S. Staffolani, S. Gaetani, V. Ciarapica, M. Amati, M. Bracci, M. Valentino, J. Goodwin, M. Nguyen, J. Truksa, M. Sobol, P. Hozak, L. F. Dong, L. Santarelli and J. Neuzil (2016). "MicroRNA-126 induces autophagy by altering cell metabolism in malignant mesothelioma." Oncotarget 7(24): 36338-36352.

  • Tomasetti, M., M. Amati, L. Santarelli and J. Neuzil (2016). "MicroRNA in Metabolic Re-Programming and Their Role in Tumorigenesis." Int J Mol Sci 17(5).

  • Vanova, K., S. Boukalova, H. Gbelcova, L. Muchova, J. Neuzil, R. Gurlich, T. Ruml and L. Vitek (2016). "Heme oxygenase is not involved in the anti-proliferative effects of statins on pancreatic cancer cells." BMC Cancer 16: 309.

  • Yan, B., L. Dong and J. Neuzil (2016). "Mitochondria: An intriguing target for killing tumour-initiating cells." Mitochondrion 26: 86-93.


  • Berridge, M. V., L. Dong and J. Neuzil (2015). "Mitochondrial DNA in Tumor Initiation, Progression, and Metastasis: Role of Horizontal mtDNA Transfer." Cancer Res 75(16): 3203-3208.

  • Khera, A., L. F. Dong, O. Holland, J. Vanderlelie, E. A. Pasdar, J. Neuzil and A. V. Perkins (2015). "Selenium supplementation induces mitochondrial biogenesis in trophoblasts." Placenta 36(8): 863-869.

  • Kluckova, K., L. F. Dong, M. Bajzikova, J. Rohlena and J. Neuzil (2015). "Evaluation of respiration of mitochondria in cancer cells exposed to mitochondria-targeted agents." Methods Mol Biol 1265: 181-194.

  • Kluckova, K., M. Sticha, J. Cerny, T. Mracek, L. Dong, Z. Drahota, E. Gottlieb, J. Neuzil and J. Rohlena (2015). "Ubiquinone-binding site mutagenesis reveals the role of mitochondrial complex II in cell death initiation." Cell Death Dis 6: e1749.

  • Koudelka, S., P. Turanek Knotigova, J. Masek, L. Prochazka, R. Lukac, A. D. Miller, J. Neuzil and J. Turanek (2015). "Liposomal delivery systems for anti-cancer analogues of vitamin E." J Control Release 207: 59-69.

  • Pasdar, E. A., M. Smits, M. Stapelberg, M. Bajzikova, M. Stantic, J. Goodwin, B. Yan, J. Stursa, J. Kovarova, K. Sachaphibulkij, A. Bezawork-Geleta, M. Sobol, A. Filimonenko, M. Tomasetti, R. Zobalova, P. Hozak, L. F. Dong and J. Neuzil (2015). "Characterisation of mesothelioma-initiating cells and their susceptibility to anti-cancer agents." Plos One 10(5): e0119549.

  • Santarelli, L., S. Staffolani, E. Strafella, L. Nocchi, N. Manzella, P. Grossi, M. Bracci, E. Pignotti, R. Alleva, B. Borghi, C. Pompili, A. Sabbatini, C. Rubini, L. Zuccatosta, E. Bichisecchi, M. Valentino, K. Horwood, M. Comar, M. Bovenzi, L. F. Dong, J. Neuzil, M. Amati and M. Tomasetti (2015). "Combined circulating epigenetic markers to improve mesothelin performance in the diagnosis of malignant mesothelioma." Lung Cancer 90(3): 457-464.

  • Tan, A. S., J. W. Baty, L. F. Dong, A. Bezawork-Geleta, B. Endaya, J. Goodwin, M. Bajzikova, J. Kovarova, M. Peterka, B. Yan, E. A. Pesdar, M. Sobol, A. Filimonenko, S. Stuart, M. Vondrusova, K. Kluckova, K. Sachaphibulkij, J. Rohlena, P. Hozak, J. Truksa, D. Eccles, L. M. Haupt, L. R. Griffiths, J. Neuzil and M. V. Berridge (2015). "Mitochondrial genome acquisition restores respiratory function and tumorigenic potential of cancer cells without mitochondrial DNA." Cell Metabolism 21(1): 81-94.

  • Tomasetti, M., L. Santarelli, R. Alleva, L. F. Dong and J. Neuzil (2015). "Redox-active and redox-silent compounds: synergistic therapeutics in cancer." Curr Med Chem 22(5): 552-568.

  • Truksa, J., L. F. Dong, J. Rohlena, J. Stursa, M. Vondrusova, J. Goodwin, M. Nguyen, K. Kluckova, Z. Rychtarcikova, S. Lettlova, J. Spacilova, M. Stapelberg, M. Zoratti and J. Neuzil (2015). "Mitochondrially targeted vitamin E succinate modulates expression of mitochondrial DNA transcripts and mitochondrial biogenesis." Antioxid Redox Signal 22(11): 883-900.

  • Vondrusova, M., A. Bezawork-Geleta, K. Sachaphibulkij, J. Truksa and J. Neuzil (2015). "The effect of mitochondrially targeted anticancer agents on mitochondrial (super)complexes." Methods Mol Biol 1265: 195-208.

  • Yan, B., M. Stantic, R. Zobalova, A. Bezawork-Geleta, M. Stapelberg, J. Stursa, K. Prokopova, L. Dong and J. Neuzil (2015). "Mitochondrially targeted vitamin E succinate efficiently kills breast tumour-initiating cells in a complex II-dependent manner." BMC Cancer 15: 401.


  • Dong, L. F. and J. Neuzil (2014). "Mitochondria in cancer: why mitochondria are a good target for cancer therapy." Prog Mol Biol Transl Sci 127: 211-227.

  • Hwang, M. S., J. Rohlena, L. F. Dong, J. Neuzil and S. Grimm (2014). "Powerhouse down: Complex II dissociation in the respiratory chain." Mitochondrion 19 Pt A: 20-28.

  • Kovarova, J., M. Bajzikova, M. Vondrusova, J. Stursa, J. Goodwin, M. Nguyen, R. Zobalova, E. A. Pesdar, J. Truksa, M. Tomasetti, L. F. Dong and J. Neuzil (2014). "Mitochondrial targeting of alpha-tocopheryl succinate enhances its anti-mesothelioma efficacy." Redox Rep 19(1): 16-25.

  • Stapelberg, M., R. Zobalova, M. N. Nguyen, T. Walker, M. Stantic, J. Goodwin, E. A. Pasdar, T. Thai, K. Prokopova, B. Yan, S. Hall, N. de Pennington, S. R. Thomas, G. Grant, J. Stursa, M. Bajzikova, A. C. B. Meedeniya, J. Truksa, S. J. Ralph, O. Ansorge, L. F. Dong and J. Neuzil (2014). "Indoleamine-2,3-dioxygenase elevated in tumor-initiating cells is suppressed by mitocans." Free Radical Biology and Medicine 67: 41-50.

  • Tomasetti, M., L. Nocchi, S. Staffolani, N. Manzella, M. Amati, J. Goodwin, K. Kluckova, M. Nguyen, E. Strafella, M. Bajzikova, M. Peterka, S. Lettlova, J. Truksa, W. Lee, L. F. Dong, L. Santarelli and J. Neuzil (2014). "MicroRNA-126 suppresses mesothelioma malignancy by targeting IRS1 and interfering with the mitochondrial function." Antioxid Redox Signal 21(15): 2109-2125.

  • Tomasetti, M., L. Santarelli, J. Neuzil and L. Dong (2014). "MicroRNA regulation of cancer metabolism: role in tumour suppression." Mitochondrion 19 Pt A: 29-38.

  • Tomasetti, M., J. Neuzil and L. Dong (2014). "MicroRNAs as regulators of mitochondrial function: role in cancer suppression." Biochim Biophys Acta 1840(4): 1441-1453.

  • Yanamala, N., A. A. Kapralov, M. Djukic, J. Peterson, G. Mao, J. Klein-Seetharaman, D. A. Stoyanovsky, J. Stursa, J. Neuzil and V. E. Kagan (2014). "Structural re-arrangement and peroxidase activation of cytochrome c by anionic analogues of vitamin E, tocopherol succinate and tocopherol phosphate." J Biol Chem 289(47): 32488-32498.


  • Kluckova, K., A. Bezawork-Geleta, J. Rohlena, L. Dong and J. Neuzil (2013). "Mitochondrial complex II, a novel target for anti-cancer agents." Biochim Biophys Acta 1827(5): 552-564.

  • Kovarova, N., T. Mracek, H. Nuskova, E. Holzerova, M. Vrbacky, P. Pecina, K. Hejzlarova, K. Kluckova, J. Rohlena, J. Neuzil and J. Houstek (2013). "High molecular weight forms of mammalian respiratory chain complex II." Plos One 8(8): e71869.

  • Moreno-Sanchez, R., L. Hernandez-Esquivel, N. A. Rivero-Segura, A. Marin-Hernandez, J. Neuzil, S. J. Ralph and S. Rodriguez-Enriquez (2013). "Reactive oxygen species are generated by the respiratory complex II--evidence for lack of contribution of the reverse electron flow in complex I." FEBS J 280(3): 927-938.

  • Neuzil, J. and R. Moreno-Sanchez (2013). "Editorial: The Bioenergetics of Cancer, the Warburg Hypothesis and the Mitochondrial Function." Curr Pharm Biotechnol 14(3): 249-250.

  • Neuzil, J., L. F. Dong, J. Rohlena, J. Truksa and S. J. Ralph (2013). "Classification of mitocans, anti-cancer drugs acting on mitochondria." Mitochondrion 13(3): 199-208.

  • Prochazka, L., S. Koudelka, L. F. Dong, J. Stursa, J. Goodwin, J. Neca, J. Slavik, M. Ciganek, J. Masek, K. Kluckova, M. Nguyen, J. Turanek and J. Neuzil (2013). "Mitochondrial targeting overcomes ABCA1-dependent resistance of lung carcinoma to alpha-tocopheryl succinate." Apoptosis 18(3): 286-299.

  • Rohlena, J., L. F. Dong and J. Neuzil (2013). "Targeting the mitochondrial electron transport chain complexes for the induction of apoptosis and cancer treatment." Curr Pharm Biotechnol 14(3): 377-389.


  • Dong, L. F., G. Grant, H. Massa, R. Zobalova, E. Akporiaye and J. Neuzil (2012). "alpha-Tocopheryloxyacetic acid is superior to alpha-tocopheryl succinate in suppressing HER2-high breast carcinomas due to its higher stability." Int J Cancer 131(5): 1052-1058.

  • Midwinter, R. G., G. J. Maghzal, J. M. Dennis, B. J. Wu, H. Cai, A. A. Kapralov, N. A. Belikova, Y. Y. Tyurina, L. F. Dong, L. Khachigian, J. Neuzil, V. E. Kagan and R. Stocker (2012). "Succinobucol induces apoptosis in vascular smooth muscle cells." Free Radic Biol Med 52(5): 871-879.

  • Neuzil, J., J. Rohlena and L.-F. Dong (2012). "K-Ras and mitochondria: Dangerous liaisons." Cell Research 22(2): 285-287.

  • Rodriguez-Enriquez, S., L. Hernandez-Esquivel, A. Marin-Hernandez, L. F. Dong, E. T. Akporiaye, J. Neuzil, S. J. Ralph and R. Moreno-Sanchez (2012). "Molecular mechanism for the selective impairment of cancer mitochondrial function by a mitochondrially targeted vitamin E analogue." Biochim Biophys Acta 1817(9): 1597-1607.

  • Tomasetti, M., L. Nocchi, J. Neuzil, J. Goodwin, M. Nguyen, L. Dong, N. Manzella, S. Staffolani, C. Milanese, B. Garrone, R. Alleva, B. Borghi, L. Santarelli and R. Guerrieri (2012). "Alpha-tocopheryl succinate inhibits autophagic survival of prostate cancer cells induced by vitamin K3 and ascorbate to trigger cell death." Plos One 7(12): e52263.


  • Dong, L. F., V. J. Jameson, D. Tilly, L. Prochazka, J. Rohlena, K. Valis, J. Truksa, R. Zobalova, E. Mahdavian, K. Kluckova, M. Stantic, J. Stursa, R. Freeman, P. K. Witting, E. Norberg, J. Goodwin, B. A. Salvatore, J. Novotna, J. Turanek, M. Ledvina, P. Hozak, B. Zhivotovsky, M. J. Coster, S. J. Ralph, R. A. Smith and J. Neuzil (2011). "Mitochondrial targeting of alpha-tocopheryl succinate enhances its pro-apoptotic efficacy: a new paradigm for effective cancer therapy." Free Radic Biol Med 50(11): 1546-1555.

  • Dong, L. F., V. J. Jameson, D. Tilly, J. Cerny, E. Mahdavian, A. Marin-Hernandez, L. Hernandez-Esquivel, S. Rodriguez-Enriquez, J. Stursa, P. K. Witting, B. Stantic, J. Rohlena, J. Truksa, K. Kluckova, J. C. Dyason, M. Ledvina, B. A. Salvatore, R. Moreno-Sanchez, M. J. Coster, S. J. Ralph, R. A. Smith and J. Neuzil (2011). "Mitochondrial targeting of vitamin E succinate enhances its pro-apoptotic and anti-cancer activity via mitochondrial complex II." J Biol Chem 286(5): 3717-3728.

  • Ito, K., S. A. Scott, S. Cutler, L. F. Dong, J. Neuzil, H. Blanchard and S. J. Ralph (2011). "Thiodigalactoside inhibits murine cancers by concurrently blocking effects of galectin-1 on immune dysregulation, angiogenesis and protection against oxidative stress." Angiogenesis 14(3): 293-307.

  • Neuzil, J., J. Cerny, J. C. Dyason, L. F. Dong and S. J. Ralph (2011). "Affinity of vitamin E analogues for the ubiquinone complex II site correlates with their toxicity to cancer cells." Mol Nutr Food Res 55(10): 1543-1551.

  • Nocchi, L., M. Tomasetti, M. Amati, J. Neuzil, L. Santarelli and F. Saccucci (2011). "Thrombomodulin is silenced in malignant mesothelioma by a poly(ADP-ribose) polymerase-1-mediated epigenetic mechanism." J Biol Chem 286(22): 19478-19488.

  • Ralph, S. J., R. Moreno-Sanchez, J. Neuzil and S. Rodriguez-Enriquez (2011). "Inhibitors of succinate: quinone reductase/Complex II regulate production of mitochondrial reactive oxygen species and protect normal cells from ischemic damage but induce specific cancer cell death." Pharm Res 28(11): 2695-2730.

  • Rohlena, J., L. F. Dong, K. Kluckova, R. Zobalova, J. Goodwin, D. Tilly, J. Stursa, A. Pecinova, A. Philimonenko, P. Hozak, J. Banerjee, M. Ledvina, C. K. Sen, J. Houstek, M. J. Coster and J. Neuzil (2011). "Mitochondrially targeted alpha-tocopheryl succinate is antiangiogenic: potential benefit against tumor angiogenesis but caution against wound healing." Antioxid Redox Signal 15(12): 2923-2935.

  • Rohlena, J., L. F. Dong, S. J. Ralph and J. Neuzil (2011). "Anticancer drugs targeting the mitochondrial electron transport chain." Antioxid Redox Signal 15(12): 2951-2974.

  • Santarelli, L., E. Strafella, S. Staffolani, M. Amati, M. Emanuelli, D. Sartini, V. Pozzi, D. Carbonari, M. Bracci, E. Pignotti, P. Mazzanti, A. Sabbatini, R. Ranaldi, S. Gasparini, J. Neuzil and M. Tomasetti (2011). "Association of MiR-126 with soluble mesothelin-related peptides, a marker for malignant mesothelioma." Plos One 6(4): e18232.

  • Tomasetti, M., M. Amati, L. Nocchi, F. Saccucci, E. Strafella, S. Staffolani, L. M. Tarquini, D. Carbonari, R. Alleva, B. Borghi, J. Neuzil, M. Bracci and L. Santarelli (2011). "Asbestos exposure affects poly(ADP-ribose) polymerase-1 activity: role in asbestos-induced carcinogenesis." Mutagenesis 26(5): 585-591.

  • Valis, K., L. Prochazka, E. Boura, J. Chladova, T. Obsil, J. Rohlena, J. Truksa, L.-F. Dong, S. J. Ralph and J. Neuzil (2011). "Hippo/Mst1 Stimulates Transcription of the Proapoptotic Mediator NOXA in a FoxO1-Dependent Manner." Cancer Research 71(3): 946-954.

  • Zobalova, R., K. Prokopova, M. Stantic, M. Stapelberg, L. F. Dong, S. J. Ralph, E. Akporiaye and J. Neuzil (2011). "The potential role of CD133 in immune surveillance and apoptosis: a mitochondrial connection?" Antioxid Redox Signal 15(12): 2989-3002.


  • Biasutto, L., L. F. Dong, M. Zoratti and J. Neuzil (2010). "Mitochondrially targeted anti-cancer agents." Mitochondrion 10(6): 670-681.

  • Koudelka, S., J. Masek, J. Neuzil and J. Turanek (2010). "Lyophilised liposome-based formulations of alpha-tocopheryl succinate: preparation and physico-chemical characterisation." J Pharm Sci 99(5): 2434-2443.

  • Prochazka, L., L. F. Dong, K. Valis, R. Freeman, S. J. Ralph, J. Turanek and J. Neuzil (2010). "alpha-Tocopheryl succinate causes mitochondrial permeabilization by preferential formation of Bak channels." Apoptosis 15(7): 782-794.

  • Ralph, S. J., S. Rodriguez-Enriquez, J. Neuzil, E. Saavedra and R. Moreno-Sanchez (2010). "The causes of cancer revisited: "mitochondrial malignancy" and ROS-induced oncogenic transformation - why mitochondria are targets for cancer therapy." Mol Aspects Med 31(2): 145-170.

  • Ralph, S. J., S. Rodriguez-Enriquez, J. Neuzil and R. Moreno-Sanchez (2010). "Bioenergetic pathways in tumor mitochondria as targets for cancer therapy and the importance of the ROS-induced apoptotic trigger." Mol Aspects Med 31(1): 29-59.

  • Tomasetti, M., E. Strafella, S. Staffolani, L. Santarelli, J. Neuzil and R. Guerrieri (2010). "alpha-Tocopheryl succinate promotes selective cell death induced by vitamin K3 in combination with ascorbate." Br J Cancer 102(8): 1224-1234.


  • Dong, L. F., R. Freeman, J. Liu, R. Zobalova, A. Marin-Hernandez, M. Stantic, J. Rohlena, K. Valis, S. Rodriguez-Enriquez, B. Butcher, J. Goodwin, U. T. Brunk, P. K. Witting, R. Moreno-Sanchez, I. E. Scheffler, S. J. Ralph and J. Neuzil (2009). "Suppression of tumor growth in vivo by the mitocan alpha-tocopheryl succinate requires respiratory complex II." Clin Cancer Res 15(5): 1593-1600.

  • Morrison, B. J., L. Andera, B. A. Reynolds, S. J. Ralph and J. Neuzil (2009). "Future use of mitocans against tumour-initiating cells?" Mol Nutr Food Res 53(1): 147-153.

  • Ralph, S. J. and J. Neuzil (2009). "Mitochondria as targets for cancer therapy." Mol Nutr Food Res 53(1): 9-28.

  • Turanek, J., X. F. Wang, P. Knotigova, S. Koudelka, L. F. Dong, E. Vrublova, E. Mahdavian, L. Prochazka, S. Sangsura, A. Vacek, B. A. Salvatore and J. Neuzil (2009). "Liposomal formulation of alpha-tocopheryl maleamide: in vitro and in vivo toxicological profile and anticancer effect against spontaneous breast carcinomas in mice." Toxicol Appl Pharmacol 237(3): 249-257.


  • Dong, L. F., P. Low, J. C. Dyason, X. F. Wang, L. Prochazka, P. K. Witting, R. Freeman, E. Swettenham, K. Valis, J. Liu, R. Zobalova, J. Turanek, D. R. Spitz, F. E. Domann, I. E. Scheffler, S. J. Ralph and J. Neuzil (2008). "Alpha-tocopheryl succinate induces apoptosis by targeting ubiquinone-binding sites in mitochondrial respiratory complex II." Oncogene 27(31): 4324-4335.

  • Zobalova, R., M. Stantic, K. Prokopova, L. F. Dong and J. Neuzil (2008). "Cancer cells with high expression of CD133 exert FLIP upregulation and resistance to TRAIL-induced apoptosis." Biofactors 34(3): 231-235.


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GACR: GJ20-11724Y, Š. Boukalová: Targeting mitochondrial metabolism in pancreatic cancer therapy. 2020-2022.

GACR: GA20-05942S, J. Neužil: Role of horizontal transfer of mitochondria in brain tumour formation. 2020-2022.

GACR: GA19-08772S, L. Anděra: Dissecting a contribution of BCL-2 family proteins to mitochondrial bioenergetics. 2019-2021.

GACR: GA19-20553S, J. Rohlena: Composition and Function of CII-low, an Alternative Assembly Form of Respiratory Complex II. 2019-2021.

GACR: GA18-10832S, J. Neužil: Molecular mechanism of mitochondrial movement between cells. 2018-2020.

GACR: GA18-02550S, S. Hubáčková: Specific elimination of senescent cells using mitochondria-targeted compounds. 2018-2020.

GACR: GA17-07635S, S. Hubáčková: Mechanisms of IFNgamma-induced cellular senescence and phenotypic plasticity. 2017-2019.

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GACR: GC17-01192J, J. Neužil: The role of mitochondrial respiration in tumour initiation and growth: A mechanistic study. 2017-2019.

AZV: 17-30138A, J. Neužil: OXPHOS Addiction as a New Hallmark in Cancer: Its Use for Development of Novel, Efficient Cancer Therapy. 2017-2020.

AZV: 16-31604A, J. Neužil: Mitochondrial targeting as efficient treatment of pancreatic cancer and type 2 diabetes mellitus. 2016-2019.

GACR: GA16-12719S, J. Neužil: Role of receptor tyrosine kinase Her2 in mitochondria. 2016-2018.

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GACR: GA15-02203S, J. Neužil: Acquisition of the mitochondrial genome by cells with damaged mitochondrial DNA restores the mitochondrial function and tumorigenic capacity. 2015-2017.

GAUK: 362015 The mechanism of mitochondria transfer in vivo. 2015-2016.

GAUK: 98215 The role of mitochondria in sensitivity of proliferating cells to oxidative stress and cell death. 2015-2016.

MH: NT14078, Inhibition of angiogenesis as an efficient way to suppress pancreatic cancer. 2013-2015.

GACR: GAP301/12/1851, J. Rohlena: Induction of apoptosis in cancer cells by mitochondria-specific compounds; the role of respiratory complex II. 2012-2014.

GACR: GAP305/12/1708, J. Truksa: Modulation of mitochondrial functions in cancer cells by the mitochondrially targeted vitamin E analogues. 2012-2014.

GAUK: 268111 The role of erbB-2 in the cancer stem cells resistance for therapy. 2011-2012.

GACR: GAP301/10/1937, J. Neužil: Mechanisms of efficient killing of cancer stem cells. 2010-2013.

ASCR: KJB500970904, K. Vališ: Molecular mechanism of apoptosis induced by alpha-tocopheryl succinate in cancer cells. 2009-2010.

GACR: GA204/08/0811, J. Neužil: Mechanism of ROS generation and mitochondrial permeabilization. 2008-2010.

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