title: Mylabris phalerlata induces apoptosis by caspase activation following cytochrome c release and Bid cleavage.
abstract: Mylabris phalerata (MP) is an insect that has been used for the treatment of cancer in oriental medicine. In the present study, the butanol (BuOH) fraction of MP (BFMP) was examined to determine whether it can exert anti-cancer activity through an apoptotic pathway with little toxicity. BFMP was found to have a specific cytotoxic effect on human monocytic leukemic U937 cells (IC(50) = 140 microg/ml) rather than on peripheral blood mononuclear lymphocytes (PBML, IC(50) = over 500 microg/ml). BFMP also induced the morphological changes of apoptosis, such as chromatin condensation, cell shrinking and DNA fragmentation at a concentration of 31.25 microg/ml. In addition, BFMP significantly increased the portion of apoptotic annexin-V positive cells in a dose-dependent manner, and effectively activated caspases (cysteine aspartase) cascade involving caspases 8, 9 and 3. BFMP also effectively cleaved Bid, a death agonist member of the Bcl-2 family and (poly(ADP-ribose)polymerase) (PARP) and induced the subsequent release of cytochrome c from mitochondria into the cytosol. However, it did not affect Bcl-2 and Bax expression. Taken together, these data suggest that the BuOH extract of Mylabris phalerata can induce apoptosis in U937 cells by caspase cascade activation in conjunction with cytochrome c release, induced by a product of Bid. Therefore, we conclude that BFMP has anti-cancer activity, which is achieved through apoptosis and is associated with little toxicity.
authors.affiliation: Department of Oncology, Graduate School of East-West Medicine, KyungHee University, 1 Seochunri, Yongin 449-701, South Korea.
authors.forename: Jeong-Eun
authors.initials: JE
authors.lastname: Huh
authors.forename: Kyung-Sun
authors.initials: KS
authors.lastname: Kang
authors.forename: Kyoo-Seok
authors.initials: KS
authors.lastname: Ahn
authors.forename: Dong-Hee
authors.initials: DH
authors.lastname: Kim
authors.forename: Ikuo
authors.initials: I
authors.lastname: Saiki
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D051023:BH3 Interacting Domain Death Agonist Protein; D002352:Carrier Proteins / Q000378:metabolism*; D020169:Caspases / Q000096:biosynthesis*; D002455:Cell Division / Q000187:drug effects; D001517:Coleoptera / Q000737:chemistry; D003574:Cytochrome c Group / Q000378:metabolism*; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020287:In Situ Nick-End Labeling; D020128:Inhibitory Concentration 50; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008516:Medicine, Chinese Traditional; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D014020:Tissue Extracts / Q000494:pharmacology*; D020298:U937 Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology
chemical_list: D017304:Annexin A5; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D002352:Carrier Proteins; D003574:Cytochrome c Group; D014020:Tissue Extracts; D020169:Caspases