title: Ginkgetin induces apoptosis via activation of caspase and inhibition of survival genes in PC-3 prostate cancer cells.
abstract: Ginkgetin is a natural biflavonoid isolated from leaves of Ginkgo biloba L. Though it was known to have anti-inflammatory, anti-influenza virus, anti-fungal activity, osteoblast differentiation stimulating activity and neuro-protective effects, the underlying antitumor mechanism of ginkgetin still remains unclear. Thus, in the present study, anti-cancer mechanism of ginkgetin was elucidated in human prostate cancer PC-3 cells. Ginkgetin suppressed the viability of PC-3 cells in a concentration-dependent manner and also significantly increased the sub-G1 DNA contents of cell cycle in PC-3 cells. Ginkgetin activated caspase-3 and attenuated the expression of survival genes such as Bcl-2, Bcl-xL, survivin and Cyclin D1 at protein and mRNA levels. Consistently, pan-caspase inhibitor Z-DEVD-fmk blocked sub G1 accumulation and cleavages of PRAP and caspase 3 induced by ginkgetin in PC-3 cells. Overall, these findings suggest that ginkgetin induces apoptosis in PC-3 cells via activation of caspase 3 and inhibition of survival genes as a potent chemotherapeutic agent for prostate cancer treatment.
authors.affiliation: College of Korean Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Ok Heui
authors.initials: OH
authors.lastname: You
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Bonglee
authors.initials: B
authors.lastname: Kim
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Sohn
authors.forename: Hyo-Jeong
authors.initials: HJ
authors.lastname: Lee
authors.forename: Bum-Sang
authors.initials: BS
authors.lastname: Shim
authors.forename: Miyong
authors.initials: M
authors.lastname: Yun
authors.forename: Byung-Mog
authors.initials: BM
authors.lastname: Kwon
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D044946:Biflavonoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D020169:Caspases / Q000737:chemistry / Q000378:metabolism*; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D020441:Ginkgo biloba / Q000737:chemistry; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D000077022:Survivin; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D044946:Biflavonoids; D051034:Inhibitor of Apoptosis Proteins; D009842:Oligopeptides; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin; D051020:bcl-X Protein; C110772:benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; D019938:Cyclin D1; C077458:ginkgetin; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases