Overexpression of apoptosis-inducing factor mitochondrion-associated 1 (AIFM1) induces apoptosis by promoting the transcription of caspase3 and DRAM in hepatoma cells.

Full-length apoptosis-inducing factor mitochondrion-associated 1 (AIFM1) (∼67 kDa) induces apoptosis in a caspase-independent manner when it is cleaved at its N-terminus to produce truncated AIFM1 (∼57 kDa). Here, we produced recombinant adenovirus AIFM1 (rAd-AIFM1) encoding full-length AIFM1 to detect whether full-length AIFM1 suppresses cell growth and induces apoptosis of hepatoma cell lines (HepG2 and Hep3B). Hepatocellular carcinoma (HCC) is one of the most difficult cancers to treat worldwide. The MTT assay demonstrated that full-length AIFM1 inhibited the growth of hepatoma cells because rAd-AIFM1 infection suppressed the proliferation of HepG2 and Hep3B cells. TUNEL assay demonstrated that full-length AIFM1 overexpression induced apoptosis in HepG2 and Hep3B cells infected with rAd-AIFM1, suggesting an apoptosis-inducing ability of full-length AIFM1. Our data further showed that the expression of two pro-apoptotic genes, caspase3 and DRAM, were involved in full-length AIFM1 infection-induced apoptosis, and full-length AIFM1 could also positively regulate the transcription of caspase3 and DRAM. Thus, overexpression of full-length AIFM1 can induce caspase-dependent apoptosis and suppresses cell growth of hepatoma cells. Our data uncover a potential role of rAd-AIFM1 in HCC gene therapy.