title: Ginkgetin exerts growth inhibitory and apoptotic effects on osteosarcoma cells through inhibition of STAT3 and activation of caspase-3/9.
abstract: Osteosarcoma is composed of tumor osteoblasts and bone-like tissues, with malignant tumors originating from osteogenesis organization. Osteosarcoma is a primary malignant bone tumor. Invasion and metastasis of osteosarcoma affect the prognosis of patients. However, effective therapeutic treatments remain to be identified. The aim of the present study was to investigate the possible inhibitory and apoptotic effects of ginkgetin in osteosarcoma cells. 3.3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays were used to determine the effect ginkgetin exerted on the growth of osteosarcoma cells. Flow cytometry was used to determine cell apoptosis. STAT3 protein expression and activation of caspase-3/9 were measured using western blot analysis and the MTT and LDH assays, respectively. The results showed that ginkgetin inhibited cell growth and induced cell cytotoxicity in osteosarcoma cells in a dose-dependent manner. Treatment with ginkgetin significantly activated the apoptosis of osteosarcoma cells in a concentration-dependent manner. The anticancer activity of ginkgetin significantly inhibited STAT3 and promoted caspase-3/9 activation in osteosarcoma cells. The findings demonstrated that ginkgetin exerts growth inhibitory and apoptotic effects on osteosarcoma cells through the inhibition of STAT3 and activation of caspase-3/9.
authors.affiliation: Department of Orthopedics Institute, Affiliated Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei 442008, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Xiong
authors.affiliation: Department of Orthopedics Institute, Affiliated Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei 442008, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Orthopedics Institute, Affiliated Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei 442008, P.R. China.
authors.forename: Hua-Long
authors.initials: HL
authors.lastname: Yu
authors.affiliation: Department of Orthopedics Institute, Affiliated Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei 442008, P.R. China.
authors.forename: Heng
authors.initials: H
authors.lastname: Han
authors.affiliation: Department of Orthopedics Institute, Affiliated Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei 442008, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Mao
authors.affiliation: Department of Orthopedics Institute, Affiliated Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei 442008, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Orthopedics Institute, Affiliated Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei 442008, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Department of Orthopedics Institute, Affiliated Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei 442008, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: He
authors.affiliation: Department of Orthopedics Institute, Affiliated Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei 442008, P.R. China.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Liu
authors.affiliation: Department of Orthopedics Institute, Affiliated Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei 442008, P.R. China.
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Wang
authors.affiliation: Department of Orthopedics Institute, Affiliated Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei 442008, P.R. China.
authors.forename: Shou-Jia
authors.initials: SJ
authors.lastname: Xu
authors.affiliation: Department of Orthopedics Institute, Affiliated Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei 442008, P.R. China.
authors.forename: Le-Yun
authors.initials: LY
authors.lastname: Guo
authors.affiliation: Department of Orthopedics Institute, Affiliated Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei 442008, P.R. China.
authors.forename: Yong-An
authors.initials: YA
authors.lastname: Wang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D044946:Biflavonoids / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism*; D053453:Caspase 9 / Q000378:metabolism*; D002455:Cell Division; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000096:biosynthesis; D004789:Enzyme Activation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D019940:Genes, bcl-1; D019254:Genes, bcl-2; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis / Q000235:genetics; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012516:Osteosarcoma / Q000473:pathology*; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000235:genetics; D000077022:Survivin; D051020:bcl-X Protein / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C494811:BCL2L1 protein, human; C107489:BIRC5 protein, human; D044946:Biflavonoids; C530104:CCND1 protein, human; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000077022:Survivin; D051020:bcl-X Protein; D019938:Cyclin D1; C077458:ginkgetin; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9