Cell-cycle arrest at G2/M and proliferation inhibition by adenovirus-expressed mitofusin-2 gene in human colorectal cancer cell lines

Abstract

The mitofusin-2 (Mfn2) is a novel gene characterised as a cell proliferation inhibitor. Mfn2 protein over-expression, mediated by an adenovirus, has a significant anti-proliferative effect in hepatoma carcinoma cells. However, there is no report on the effect of Mfn2 on colorectal cancer (CRC). In this study, we found that Mfn2 protein and mRNA levels were downregulated in CRC tissues compared to nearby normal tissues. An adenovirus encoding the complete Mfn2 open reading frame (Ad-Mfn2) exhibited a prominent anti-proliferative effect in the CRC cell lines HCT 116, HT-29, and SW480. Ad- Mfn2 infection significantly inhibited the proliferation of CRC cells compared with Ad-GFP infection. Mfn2 overexpression resulted in a cell-cycle arrest at G2/M phase in CRC cells, and it increased the levels of p-cdc2 (Tyr15) and Myt1; however, the levels of cyclin B1 and p-ERK1/2 was reduced. Mfn2 overexpression aslo increased the levels of active caspase-3 and cleaved PARP. Taken together, these findings indicate that Mfn2 has a significant anti-proliferative effect in CRC cells using adenoviral vectors.