Role of Bax/Bcl-2 family members in green tea polyphenol induced necroptosis of p53-deficient Hep3B cells.
Green tea polyphenol (GTP) is one of the most promising chemopreventive agent for cancer; it can inhibit cancer cell proliferation and induce apoptosis through p53-dependent cell signaling pathways. Unfortunately, many tumor cells lack the functional p53, and little is known about the effect of GTP on the p53-deficient/mutant cancer cells. To understand the p53-independent mechanisms in GTP-treated p53-dificient/mutant cancer cells, we have now examined GTP-induced cytotoxicity in human hepatoma Hep3B cells (p53-deficient). The results showed that GTP could induce Bax and Bak activation, cytochrome c release, caspase activation, and necroptosis of Hep3B cells. Bax and Bak, two key molecules of mitochondrial permeability transition pore (MPTP), were interdependently activated by GTP, with translocation and homo-oligomerization on the mitochondria. Bax and Bak induce cytochrome c release. Importantly, cytochrome c release and necroptosis were diminished in Hep3B cells (Bax(-/-)) and Hep3B cells (Bak(-/-)). Furthermore, overexpression of Bcl-2 could ameliorate GTP-induced cytochrome c release and necroptosis. Together, the findings suggested that GTP-induced necroptosis was modulated by the p53-independent pathway, which was related to the translocation of Bax and Bak to mitochondria, release of cytochrome c, and activation of caspases.
School of Pharmacy and Bioscience, Weifang Medical University, Weifang, 261000, Shandong Province, China, weipinglin_2014@163.com.
Weiping
W
Lin
Sun
S
Tongyi
D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D059808:Polyphenols / Q000494:pharmacology*; D013662:Tea / Q000737:chemistry*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000737:chemistry / Q000502:physiology*; D051028:bcl-2-Associated X Protein / Q000737:chemistry / Q000502:physiology*
C494772:BAK1 protein, human; C494826:BAX protein, human; D059808:Polyphenols; C495901:TP53 protein, human; D013662:Tea; D016159:Tumor Suppressor Protein p53; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D020169:Caspases