Tumor Biology

, Volume 35, Issue 8, pp 8065–8075 | Cite as

Role of Bax/Bcl-2 family members in green tea polyphenol induced necroptosis of p53-deficient Hep3B cells

  • Weiping LinEmail author
  • Sun Tongyi
Research Article


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.


GTP Hep3B cells Bax Bcl-2 Necroptosis 



Green tea polyphenol


Dimethyl sulfoxide


Bcl-2-associated X protein


Bcl-2 antagonist killer


Mitochondrial permeability transition pore



This work was supported by grants from Science Technology Study of Hubei Department of Education Foundation (No. Q20132804). Chinese National Natural Science Foundation (81102363); and the Scientific Research Foundation for the Excellent Middle-Aged and Youth Scientists of Shandong Province of China (BS2012YY037).


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  1. 1.School of Pharmacy and BioscienceWeifang Medical UniversityWeifangChina

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