title: Effects of α-mangostin on apoptosis induction of human colon cancer.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Srinakharinwirot University, Bangkok 10110, Thailand. ramidawa@yahoo.com
authors.forename: Ramida
authors.initials: R
authors.lastname: Watanapokasin
authors.forename: Faongchat
authors.initials: F
authors.lastname: Jarinthanan
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Nitisak
authors.initials: N
authors.lastname: Sawasjirakij
authors.forename: Amornmart
authors.initials: A
authors.lastname: Jaratrungtawee
authors.forename: Sunit
authors.initials: S
authors.lastname: Suksamrarn
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D044004:Xanthones / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D047428:Protein Kinase Inhibitors; D044004:Xanthones; D045304:Cytochromes c; D020169:Caspases; C021053:mangostin