Original Article
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Apr 28, 2011; 17(16): 2086-2095
Published online Apr 28, 2011. doi: 10.3748/wjg.v17.i16.2086
Effects of α-mangostin on apoptosis induction of human colon cancer
Ramida Watanapokasin, Faongchat Jarinthanan, Yukio Nakamura, Nitisak Sawasjirakij, Amornmart Jaratrungtawee, Sunit Suksamrarn
Ramida Watanapokasin, Department of Biochemistry, Faculty of Medicine, Srinakharinwirot University, Bangkok 10110, Thailand
Faongchat Jarinthanan, Faculty of Medical Technology, Rangsit University, Pratumthani 12130, Thailand
Yukio Nakamura, Clinical Research Center, Murayama Medical Center, Gakuen 2-37-1, Tokyo 208-0011, Japan
Nitisak Sawasjirakij, Department of Research, North Bangkok University, Bangkok 10220, Thailand
Amornmart Jaratrungtawee, Sunit Suksamrarn, Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok 10110, Thailand
Author contributions: Watanapokasin R conceived, initiated the project and designed the research, provided project guidance and supervision and wrote the paper; Jarinthanan F performed the experiments; Nakamura Y and Sawasjirakij N revised the manuscript and analyzed the data; Jaratrungtawee A and Suksamrarn S participated in purifying of the α-mangostin.
Supported by The Thailand Research Fund, Grant No. RMU 4980043
Correspondence to: Ramida Watanapokasin, PhD, Associate Professor and Head, Department of Biochemistry, Faculty of Medicine, Srinakharinwirot University, Sukhumvit 23, Bangkok 10110, Thailand. ramidawa@yahoo.com
Telephone: +66-2-6495369 Fax: +66-2-6495834
Received: November 11, 2010
Revised: January 10, 2011
Accepted: January 17, 2011
Published online: April 28, 2011
Abstract

AIM: To investigate the effect of α-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 α-mangostin to determine the effect on cell proliferation by MTT assay, cell morphology, chromatin condensation, cell cycle analysis, DNA fragmentation, phosphatidylserine exposure and changing of mitochondrial membrane potential. The molecular mechanisms of α-mangostin mediated apoptosis were further investigated by Western blotting analysis including activation of caspase cascade, cytochrome c release, Bax, Bid, p53 and Bcl-2 modifying factor.

RESULTS: The highest inhibitory effect of α-mangostin on cell proliferation of COLO 205, MIP-101 and SW 620 were 9.74 ± 0.85 μg/mL, 11.35 ± 1.12 μg/mL and 19.6 ± 1.53 μg/mL, respectively. Further study showed that α-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 α-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 α-mangostin (P < 0.01).

CONCLUSION: α-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.

Keywords: α-mangostin; Apoptosis; Caspases; Colon cancer; Mitochondria