title: Crude extract of Rheum palmatum L. Induces cell cycle arrest S phase and apoptosis through mitochondrial-dependent pathways in U-2 OS human osteosarcoma cells.
abstract: Cancer is the second cause of death in children. Osteosarcoma is the most common primary malignancy of solid bone cancer primarily affecting adolescents and young adults. In the Chinese population, the crude extract of Rheum palmatum L. (CERP) has been used for treating different diseases, including SARS, rheumatoid arthritis, coxsackievirus B3, and human colon cancer cell, pancreatic cancer. There are no reports on CERP and human osteosarcoma cells. The present study examined effects of CERP on cytotoxicity including cell cycle distribution and cell death (apoptosis) in U-2 OS human osteosarcoma cells. CERP significantly induced S phase arrest in U-2 OS cells in a dose-dependent. CERP produced DNA damage and DNA condensation. Other effects of CERP were stimulation of ROS and Ca(2+) , mitochondria impairment, and activation of caspase-3, -8, and -9. CERP increased the levels of Bax, Bak, Bad, cyclin B, Fas, PARP, GRP78, GADD153, AIF, Endo G, Calpain-2, p21, and p27, but decreased the levels of Bcl-2, BCL-X, XIAP, Akt, CDC25A, CDK2, Cyclin A, and Cyclin E of U-2 OS cells. It was also observed that CERP promoted the expression of AIF, Endo G, GADD153, and cytochrome c. These results indicate that CERP has anticancer effects in vitro and provide the foundation for in vivo studies of animal models of osteosarcoma. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 957-969, 2016.
authors.affiliation: Department of Chinese Medicine, Feng-Yuan Hospital, Ministry of Health and Welfare, Executive Yuan, Taichung, 420, Taiwan.|General Education Center, Central Taiwan University of Science and Technology, Taichung, 406, Taiwan.
authors.forename: Chin-Chung
authors.initials: CC
authors.lastname: Lin
authors.affiliation: General Education Center, Central Taiwan University of Science and Technology, Taichung, 406, Taiwan.|Department of Urology, Feng-Yuan Hospital, Ministry of Health and Welfare, Executive Yuan, Taichung, 420, Taiwan.
authors.forename: Ming-Huei
authors.initials: MH
authors.lastname: Lee
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, 404, Taiwan.
authors.forename: Ju-Hwa
authors.initials: JH
authors.lastname: Lin
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan.
authors.forename: Meng-Liang
authors.initials: ML
authors.lastname: Lin
authors.affiliation: Department of Health and Nutrition Biotechnology, Asia University, Taichung, 413, Taiwan.
authors.forename: Fu-Shin
authors.initials: FS
authors.lastname: Chueh
authors.affiliation: School of Pharmacy, China Medical University, Taichung, 404, Taiwan.
authors.forename: Chien-Chih
authors.initials: CC
authors.lastname: Yu
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung, 404, Taiwan.
authors.forename: Jing-Pin
authors.initials: JP
authors.lastname: Lin
authors.affiliation: Division of Neurosurgical Oncology, Neurological Institute, Taichung Veterans General Hospital, Taichung, 407, Taiwan.|Institute of Medical Sciences, Tzu Chi University, Hualien, 970, Taiwan.
authors.forename: Yu-Cheng
authors.initials: YC
authors.lastname: Chou
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, 404, Taiwan.
authors.forename: Shu-Chun
authors.initials: SC
authors.lastname: Hsu
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, 404, Taiwan.|Department of Biotechnology, Asia University, Taichung, 413, Taiwan.
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001859:Bone Neoplasms / Q000188:drug therapy / Q000473:pathology; D020013:Calcium Signaling; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D004354:Drug Screening Assays, Antitumor; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D012516:Osteosarcoma / Q000188:drug therapy / Q000473:pathology; D021381:Protein Transport; D017382:Reactive Oxygen Species / Q000378:metabolism; D012250:Rheum / Q000737:chemistry; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D004365:Drugs, Chinese Herbal; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D017382:Reactive Oxygen Species
keywords: apoptosis; cell cycle arrest; crude extract of Rheum palmatum L. (CERP); human osteosarcoma cells U-2 OS