Home — Research — Laboratory of Molecular Therapy
Laboratory of Molecular Therapy
Head: Prof. Jiří Neužil, PhD
Research fellows and assistants:
Jana Novotná, PhD
Jakub Rohlena, PhD
Jaroslav Truksa, PhD (from July 1, 2009)
Karel Vališ, MSc
Renata Zobalová, MSc
PhD students:
Jaromíra Chladová, MSc
Katarína Kľučková, MSc
Ľubica Škultétyová, MSc
Undergraduate students:
Kateřina Prokopová
Jana Spáčilová
Research Topics
We are focusing on the design and development of novel anticancer agents, in particular, vitamin E analogues, that are efficient and selective for malignant cells. We are especially interested in the molecular mechanism of apoptosis caused by such agents, which include pathways of mitochondrial destabilisation. We have started studying the role of mitochondria in resistance of cancer stem cells to therapy and how to overcome this.
Most important recent papers
(names of lab members underlined)
Neuzil J, Weber T, Gellert N, Weber C (2001) Selective cancer cell killing by α-tocopheryl succinate. Br J Cancer 84, 87-89.
Neuzil J, Weber T, Schröder A, Lu M, Ostermann G, Gellert N, Mayne GC, Olejnicka B, Nègre-Salvayre A, Sticha M, Coffey RJ, Weber C (2001) Induction of apoptosis in cancer cells by α-tocopheryl succinate: Molecular pathways and structural requirements. FASEB J 15, 403-415.
Neuzil J, Schröder A, von Hundelshausen P, Zernecke A, Weber T, Gellert N, Weber C (2001) Inhibition of inflammatory endothelial responses by a pathway involving caspase activation and p65 cleavage. Biochemistry 40, 4686-4692.
Neuzil J, Zhao M, Ostermann G, Sticha M, Gellert N, Weber C, Eaton JW, Brunk UT (2002) α-Tocopheryl succinate, an agent with in vivo anti-tumour activity, induces apoptosis by causing lysosomal instability. Biochem J 362, 709-715.
Weber T, Lu M, Andera L, Lahm H, Gellert N, Fariss MW, Korinek V, Sattler W, Ucker DS, Terman A, Schröder A, Erl W, Brunk U, Coffey RJ, Weber C, Neuzil J (2002) Vitamin E succinate is a potent novel anti-neoplastic agent with high tumor selectivity and cooperativity with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL, Apo2L) in vivo. Clin Cancer Res 8, 863-869.
Weber T, Dalen H, Andera L, Nègre-Salvayre A, Augé N, Sticha M, Loret A, Terman A, Witting PK, Higuchi M, Plasilova M, Zivny J, Gellert N, Weber C, Neuzil J (2003) Mitochondria play a central role in apoptosis induced by α-tocopheryl succinate, an agent with anticancer activity. Comparison with receptor-mediated pro-apoptotic signaling. Biochemistry 42, 4277-4291.
Erl W, Weber C, Zernecke A, Neuzil J, Vosseler CA, Kim HJ, Weber PC (2004) Cyclopentanone prostaglandins induce endothelial cell apoptosis independent of peroxisome proliferator activated receptor-γ. Eur J Immunol 34, 241-250.
Tomasetti M, Gellert N, Procopio A, Neuzil J (2004) A vitamin E analogue suppresses malignant mesothelioma in a pre-clinical model: A prototype of a future drug against a fatal neoplastic disease? Int J Cancer 109, 641-642.
Stapelberg M, Gellert N, Swettenham E, Tomasetti M, Witting PK, Procopio A, Neuzil J (2005) α-Tocopheryl succinate inhibits malignant mesothelioma by disrupting the FGF autocrine loop: The role of oxidative stress. J Biol Chem 280, 25369-25376.
Swettenham E, Witting PK, Salvatore BA, Neuzil J (2005) α-Tocopheryl succinate selectively induces apoptosis in neuroblastoma cells: Potential therapy of malignancies of the nervous system? J Neurochem 94, 1448-1456.
Tomic-Vatic A, EyTina JH, Chapmann JM, Mahdavian E, Neuzil J, Salvatore BA (2005) Vitamin E amides, a new class of vitamin E analogues with enhanced pro-apoptotic activity. Int J Cancer 117, 118-123.
Neuzil J, Wang XF, Dong LF, Low P, Ralph SJ (2006) Molecular mechanism of ‘mitocan’-induced apoptosis in cancer cells epitomizes the multiple roles of reactive oxygen species and Bcl-2 family proteins. FEBS Lett 580, 5125-5129.
Wang XF, Birringer M, Dong LF, Veprek P, Low P, Swettenham E, Stantic M, Yuan LH, Zobalova R, Wu K, Ralph SJ, Ledvina M, Neuzil J (2007) A peptide adduct of vitamin E succinate targets breast cancer cells with high erbB2 expression. Cancer Res 67, 3337-3344.
Neuzil J, Dyason JC, Freeman R, Dong LF, Prochazka L, Wang XF, Scheffler IE, Ralph SJ (2007) Mitocans as anti-cancer agents targeting mitochondria: Lessons from studies with vitamin E analogues, inhibitors of complex II. J Bioenerg Biomembr 39, 65-72.
Neuzil J, Swettenham E, Wang XF, Dong LF, Stapelberg M (2007) α-Tocopheryl succinate inhibits angiogenesis by disrupting paracrine FGF2 signalling. FEBS Lett 581, 5611-5615.
Neuzil J, Dong LF, Ramanathapuram L, Hahn T, Chladova M, Wang XF, Zobalova R, Prochazka L, Gold M, Freeman RE, Turanek J, Akporiaye ET, Dyason J, Ralph SJ (2007) Vitamin E analogues: a novel group of mitocans, anti-cancer agents that act by targeting mitochondria. Mol Aspects Med 28,607-645.
Dong LF, Swettenham E, Eliasson J, Wang XF, Gold M, Medunic Y, Stantic M, Low P, Prochazka L, Witting PK, Turanek J, Akporiaye ET, Ralph SJ, Neuzil J (2007) Vitamin E analogs inhibit angiogenesis by selective apoptosis induction in proliferating endothelial cells: The role of oxidative stress. Cancer Res 67, 11906-11913.
Amati M, Tomasetti M, Scarrozzi M, Mariotti L, Alleva R, Pienotti E, Borghi B, Valentino M, Governa M, Neuzil J, Santarelli L (2008) Profiling tumour-associated markers for early detection of malignant mesothelioma: an epidemiological study. Cancer Epidemiol Biomarkers Prev 17, 163-170.
Dong LF, Low P, Dyason J, Wang XF, Prochazka L, Witting PK, Freeman R, Swettenham E, Valis K, Liu J, Zobalova R, Turanek J, Spitz DR, Domann FE, Scheffler IE, Ralph SJ, Neuzil J (2008) α-Tocopheryl succinate induces apoptosis by targeting ubiquinone-binding sites in mitochondrial respiratory complex II. Oncogene 27, 4324-4335.
Zobalova R, Mc Dermott L, Stantic M, Prokopova K, Dong LF, Neuzil J (2008) CD133-positive cells are resistant to TRAIL due to up-regulation of FLIP. Biochem Biophys Res Commun 373, 567-571.
Zobalova R, Swettenham E, Chladova J, Dong LF, Neuzil J (2008) Daxx inhibits stress-induced apoptosis in cardiac myocytes. Redox Report 13, 263-270.
Ralph SJ, Neuzil J (2009) Mitocans, a class of emerging anti-cancer drugs. Mol Nutr Food Res 53, 7-8. Editorial.
Ralph SJ, Neuzil J (2009) Mitochondria as targets for cancer therapy. Mol Nutr Food Res 53, 9-28.
Zhao Y, Neuzil J, Wu K (2009) Vitamin E analogues as mitochondria-targeting compounds: From the bench to the bedside? Mol Nutr Food Res 53, 129-139.
Morrison BJ, Andera L, Reynolds BA, Ralph SJ, Neuzil J (2009) Future use of mitocans against tumour-initiating cells? Mol Nutr Food Res 53, 147-153.
Tomasetti M, Amati M, Santarelli L, Alleva R, Neuzil J (2009) Malignant mesothelioma: Biology, diagnosis and new therapeutic approaches. Curr Mol Pharmacol. Invited review (in press).
Dong LF, Freeman R, Liu J, Zobalova R, Marin-Hernandez A, Stantic M, Rohlena J, Valis K, Rodriguez-Enriquez S, Butcher B, Goodwin J, Brunk UT, Witting PK, Moreno-Sanchez R, Scheffler IE, Ralph SJ, Neuzil J (2009) Suppression of tumor growth in vivo by the mitocan α-tocopheryl succinate requires respiratory complex II. Clin Cancer Res 15, 1593-1600.