Overexpression of Bcl-2 enhances LIGHT- and interferon-γ-mediated apoptosis in Hep3BT2 cells

Mei Chieh Chen, Tsui Ling Hsu, Tien Yau Luh, Shie Liang Hsieh

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43 Citations (Scopus)


LIGHT is a member of the tumor necrosis factor superfamily and is the ligand for LT-βR, HVEM, and decoy receptor 3. LIGHT has a cytotoxic effect, which is further enhanced by the presence of interferon-γ (IFN-γ). Although LIGHT/IFN-γ can activate caspase activity, neither benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethylketone nor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone can completely inhibit LIGHT/IFN-γ-mediated apoptosis. Moreover, overexpression of Bcl-2 further enhances LIGHT/IFN-γ-mediated apoptosis. It appears that LIGHT and IFN-γ act synergistically to activate caspase-3, with the resultant cleavage of Bcl-2, removal of the BH4 domain, leading to conversion of Bcl-2 from an antiapoptotic to a proapoptotic form in p53-deficient hepatocellular carcinoma Hep3BT2 cells. Thus, LIGHT seems to be able to override the protective effect of Bcl-2 and induce cell death. Although benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethylketone and benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone can prevent the cleavage of Bcl-2 by LIGHT/IFN-γ, they only partially inhibit apoptosis in Hep3BT2 cells that are overexpressing Bcl-2. In contrast, both LIGHT/IFN-γ-mediated apoptosis and Bcl-2 cleavage are inhibited by free radical scavengers, indicating that free radicals may play an essential role in LIGHT/IFN-γ-mediated apoptosis at a step upstream of caspase-3 activation. These results suggest that LIGHT signaling may diverge into multiple, separate processes.

Original languageEnglish
Pages (from-to)38794-38801
Number of pages8
JournalJournal of Biological Chemistry
Issue number49
Publication statusPublished - Dec 8 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry


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