Mitochondrial Pathway of α-Tocopheryl Succinate-Induced Apoptosis in Human Epidermoid Carcinoma A431 Cells

Overview

Journal Acta Naturae

Specialty Biology

Date 2012 Nov 15

PMID 23150807

Authors

M A Savitskaya

M S Vildanova

O P Kisurina-Evgenieva

E A Smirnova

G E Onischenko

Affiliations

Soon will be listed here.

Abstract

Vitamin E derivatives are known to act as agents exhibiting cytotoxity against tumor cells. The effect of vitamin E succinate on human epidermoid carcinoma cell line A431 was investigated in this study using live imaging, immunocytochemistry, and transmission electron microscopy. α-Tocopheryl succinate-induced apoptotic cell death in A431 cells was shown to be both dose- and time-dependent. The hyperproduction of reactive oxygen species, changes in size, shape and ultrastructural characteristics of mitochondria followed by the release of cytochromecfrom mitochondria to cytosol were observed. These results suggest that α-tocopheryl succinate induces apoptosis that occurs via the mitochondrial pathway. Mitochondria are shown to be crucial targets in α-tocopheryl succinate-induced caspase-dependent cell death in human carcinoma A431 cells.

References

Malafa M, Fokum F, Smith L, Louis A . Inhibition of angiogenesis and promotion of melanoma dormancy by vitamin E succinate. Ann Surg Oncol. 2002; 9(10):1023-32. DOI: 10.1007/BF02574523. View

Min J, Guo J, Zhao F, Cai D . [Effect of apoptosis induced by different vitamin E homologous analogues in human hepatoma cells(HepG2)]. Wei Sheng Yan Jiu. 2003; 32(4):343-5. View

Dong L, Freeman R, Liu J, Zobalova R, Marin-Hernandez A, Stantic M . Suppression of tumor growth in vivo by the mitocan alpha-tocopheryl succinate requires respiratory complex II. Clin Cancer Res. 2009; 15(5):1593-600. DOI: 10.1158/1078-0432.CCR-08-2439. View

Wu K, Zhao Y, Liu B, Li Y, Liu F, Guo J . RRR-alpha-tocopheryl succinate inhibits human gastric cancer SGC-7901 cell growth by inducing apoptosis and DNA synthesis arrest. World J Gastroenterol. 2002; 8(1):26-30. PMC: 4656619. DOI: 10.3748/wjg.v8.i1.26. View

Dong L, Swettenham E, Eliasson J, Wang X, Gold M, Medunic Y . Vitamin E analogues inhibit angiogenesis by selective induction of apoptosis in proliferating endothelial cells: the role of oxidative stress. Cancer Res. 2007; 67(24):11906-13. DOI: 10.1158/0008-5472.CAN-07-3034. View

Theriault R, Lipton A, Hortobagyi G, Leff R, Gluck S, Stewart J . Pamidronate reduces skeletal morbidity in women with advanced breast cancer and lytic bone lesions: a randomized, placebo-controlled trial. Protocol 18 Aredia Breast Cancer Study Group. J Clin Oncol. 1999; 17(3):846-54. DOI: 10.1200/JCO.1999.17.3.846. View

Dong L, Low P, Dyason J, Wang X, PROCHAZKA L, Witting P . Alpha-tocopheryl succinate induces apoptosis by targeting ubiquinone-binding sites in mitochondrial respiratory complex II. Oncogene. 2008; 27(31):4324-35. PMC: 2668987. DOI: 10.1038/onc.2008.69. View

Kang Y, Lee E, Choi M, Ku J, Kim S, Park Y . Role of reactive oxygen species in the induction of apoptosis by alpha-tocopheryl succinate. Int J Cancer. 2004; 112(3):385-92. DOI: 10.1002/ijc.20424. View

Neuzil J, Wang X, Dong L, Low P, Ralph S . Molecular mechanism of 'mitocan'-induced apoptosis in cancer cells epitomizes the multiple roles of reactive oxygen species and Bcl-2 family proteins. FEBS Lett. 2006; 580(22):5125-9. DOI: 10.1016/j.febslet.2006.05.072. View

10.

DAlessio M, De Nicola M, Coppola S, Gualandi G, Pugliese L, Cerella C . Oxidative Bax dimerization promotes its translocation to mitochondria independently of apoptosis. FASEB J. 2005; 19(11):1504-6. DOI: 10.1096/fj.04-3329fje. View

11.

Neuzil J, Zhao M, Ostermann G, Sticha M, Gellert N, Weber C . Alpha-tocopheryl succinate, an agent with in vivo anti-tumour activity, induces apoptosis by causing lysosomal instability. Biochem J. 2002; 362(Pt 3):709-15. PMC: 1222436. DOI: 10.1042/0264-6021:3620709. View

12.

Alleva R, Benassi M, Pazzaglia L, Tomasetti M, Gellert N, Borghi B . Alpha-tocopheryl succinate alters cell cycle distribution sensitising human osteosarcoma cells to methotrexate-induced apoptosis. Cancer Lett. 2006; 232(2):226-35. DOI: 10.1016/j.canlet.2005.02.019. View

13.

Neuzil J, Weber T, Gellert N, Weber C . Selective cancer cell killing by alpha-tocopheryl succinate. Br J Cancer. 2001; 84(1):87-9. PMC: 2363620. DOI: 10.1054/bjoc.2000.1559. View

14.

Shiau C, Huang J, Wang D, Weng J, Yang C, Lin C . alpha-Tocopheryl succinate induces apoptosis in prostate cancer cells in part through inhibition of Bcl-xL/Bcl-2 function. J Biol Chem. 2006; 281(17):11819-25. DOI: 10.1074/jbc.M511015200. View

15.

Bellezza I, Tucci A, Galli F, Grottelli S, Mierla A, Pilolli F . Inhibition of NF-κB nuclear translocation via HO-1 activation underlies α-tocopheryl succinate toxicity. J Nutr Biochem. 2012; 23(12):1583-91. DOI: 10.1016/j.jnutbio.2011.10.012. View

16.

Charpentier A, Groves S, Turley J, Zhao B, Sanders B, Kline K . RRR-alpha-tocopheryl succinate inhibits proliferation and enhances secretion of transforming growth factor-beta (TGF-beta) by human breast cancer cells. Nutr Cancer. 1993; 19(3):225-39. DOI: 10.1080/01635589309514254. View

17.

Neuzil J, Svensson I, Weber T, Weber C, Brunk U . alpha-tocopheryl succinate-induced apoptosis in Jurkat T cells involves caspase-3 activation, and both lysosomal and mitochondrial destabilisation. FEBS Lett. 1999; 445(2-3):295-300. DOI: 10.1016/s0014-5793(99)00141-6. View

18.

Wang X, Witting P, Salvatore B, Neuzil J . Vitamin E analogs trigger apoptosis in HER2/erbB2-overexpressing breast cancer cells by signaling via the mitochondrial pathway. Biochem Biophys Res Commun. 2004; 326(2):282-9. DOI: 10.1016/j.bbrc.2004.11.028. View

19.

Petrova G . [Proapoptotic action of alpha-tocopheryl succinate in rat thymocytes is conditioned by the inhibition of mitochondrial succinate dehydrogenase]. Ukr Biokhim Zh (1999). 2007; 78(4):104-11. View

20.

Prochazka L, Dong L, Valis K, Freeman R, Ralph S, Turanek J . alpha-Tocopheryl succinate causes mitochondrial permeabilization by preferential formation of Bak channels. Apoptosis. 2010; 15(7):782-94. DOI: 10.1007/s10495-010-0482-z. View