Effects of α-mangostin on apoptosis induction of human colon cancer

AIM: To investigate the effect of alpha-mangostin on the growth and apoptosis induction of human colon cancer cells. METHODS: The three colorectal adenocarcinoma cell lines tested (COLO 205, MIP-101 and SW 620) were treated with alpha-mangostin to determine the effect on cell proliferation by MIT assay, cell morphology, chromatin condensation, cell cycle analysis, DNA fragmentation, phosphatidylserine exposure and changing of mitochondrial membrane potential. The molecular mechanisms of alpha-mangostin mediated apoptosis were further investigated by Western blotting analysis including activation of caspase cascade, cytochrome c release, Bax, Bid, p53 and BcI-2 modifying factor. RESULTS: The highest inhibitory effect of alpha-mangostin on cell proliferation of COLO 205, MIP-101 and SW 620 were 9.74 +/- 0.85 mu g/mL, 11.35 +/- 1.12 mu g/mL and 19.6 +/- 1.53 mu g/mL, respectively. Further study showed that alpha-mangostin induced apoptotic cell death in COLO 205 cells as indicated by membrane blebbing, chromatin condensation, DNA fragmentation, cell cycle analysis, sub-G1 peak (P < 0.05) and phosphatidylserine exposure. The executioner caspase, caspase-3, the initiator caspase, caspase-8, and caspase-9 were expressed upon treatment with alpha-mangostin. Further studies of apoptotic proteins were determined by Western blotting analysis showing increased mitochondrial cytochrome c release, Bax, p53 and Bmf as well as reduced mitochondrial membrane potential (P < 0.05). In addition, up-regulation of tBid and Fas were evident upon treatment with alpha-mangostin (P < 0.01). CONCLUSION: alpha-Mangostin may be effective as an anti-cancer agent that induced apoptotic cell death in COLO 205 via a link between extrinsic and intrinsic pathways. (C) 2011 Baishideng. All rights reserved.