title: Anemone altaica Induces Apoptosis in Human Osteosarcoma Cells.
abstract: In the past decade, no significant improvement has been made in chemotherapy for osteosarcoma (OS). To develop improved agents against OS, we screened 70 species of medicinal plants and treated two human OS cell lines with different agent concentrations. We then examined cell viability using the MTT assay. Results showed that a candidate plant, particularly the rhizomes of Anemone altaica Fisch. ex C. A. Mey aqueous extract (AAE), suppressed the viability of HOS and U2OS cells in a concentration-dependent manner. Flow cytometry analysis revealed that AAE significantly increased the amount of cell shrinkage (Sub-G1 fragments) in HOS and U2OS cells. Moreover, AAE increased cytosolic cytochrome c and Bax, but decreased Bcl-2. The amount of cleaved caspase-3 and poly-(ADP-ribose) polymerase-1 (PARP-1) were significantly increased. AAE suppressed the growth of HOS and U2OS through the intrinsic apoptotic pathway. Data suggest that AAE is cytotoxic to HOS and U2OS cells and has no significant influence on human osteoblast hFOB cells. The high mRNA levels of apoptosis-related factors (PPP1R15A, SQSTM1, HSPA1B, and DDIT4) and cellular proliferation markers (SKA2 and BUB1B) were significantly altered by the AAE treatment of HOS and U2OS cells. Results show that the anticancer activity of AAE could up-regulate the expression of a cluster of genes, especially those in the apoptosis-related factor family and caspase family. Thus, AAE has great potential as a useful therapeutic drug for human OS.
authors.affiliation: School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.|Department of Orthopedic Surgery, Chung Shan Medical University, Taichung 402, Taiwan.
authors.forename: I-Chang
authors.initials: IC
authors.lastname: Chang
authors.affiliation: Department of Nursing, College of Medicine & Nursing, Hungkuang University, Taichung 433, Taiwan.
authors.forename: Tsay-I
authors.initials: TI
authors.lastname: Chiang
authors.affiliation: Graduate Institute of Cancer Biology, China Medical University, Taichung 40402, Taiwan.
authors.forename: Chun
authors.initials: C
authors.lastname: Lo
authors.affiliation: Department of Biotechnology, Asia University, Taichung 413, Taiwan.
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Lai
authors.affiliation: Department of Surgery, Tungs' Taichung MetroHarbor Hospital, Taichung 435, Taiwan.
authors.forename: Chia-Herng
authors.initials: CH
authors.lastname: Yue
authors.affiliation: Graduate Institute of Cancer Biology, China Medical University, Taichung 40402, Taiwan.|Center for Molecular Medicine, China Medical University Hospital, Taichung 40402, Taiwan.
authors.forename: Jer-Yuh
authors.initials: JY
authors.lastname: Liu
authors.affiliation: Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan.|Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 40201, Taiwan.
authors.forename: Li-Sung
authors.initials: LS
authors.lastname: Hsu
authors.affiliation: Center for Molecular Medicine, China Medical University Hospital, Taichung 40402, Taiwan.
authors.forename: Chia-Jen
authors.initials: CJ
authors.lastname: Lee
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D031883:Anemone / Q000737:chemistry*; D000972:Antineoplastic Agents, Phytogenic; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics*; D053148:Caspase 3 / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D054645:Protein Phosphatase 1 / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D000071456:Sequestosome-1 Protein; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000972:Antineoplastic Agents, Phytogenic; C584279:BUB1B protein, human; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C469991:DDIT4 protein, human; D018840:HSP70 Heat-Shock Proteins; C525621:HSPA1B protein, human; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; C516428:SKA2 protein, human; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D014157:Transcription Factors; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D017346:Protein Serine-Threonine Kinases; C087519:PPP1R15A protein, human; D054645:Protein Phosphatase 1; D053148:Caspase 3
keywords: Anemone altaica; Apoptosis; Osteosarcoma