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Environ Toxicol. 2016 Aug;31(8):957-69. doi: 10.1002/tox.22105. Epub 2015 Feb 17.

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.

Author information

1
Department of Chinese Medicine, Feng-Yuan Hospital, Ministry of Health and Welfare, Executive Yuan, Taichung, 420, Taiwan.
2
General Education Center, Central Taiwan University of Science and Technology, Taichung, 406, Taiwan.
3
Department of Urology, Feng-Yuan Hospital, Ministry of Health and Welfare, Executive Yuan, Taichung, 420, Taiwan.
4
Department of Biological Science and Technology, China Medical University, Taichung, 404, Taiwan.
5
Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan.
6
Department of Health and Nutrition Biotechnology, Asia University, Taichung, 413, Taiwan.
7
School of Pharmacy, China Medical University, Taichung, 404, Taiwan.
8
School of Chinese Medicine, China Medical University, Taichung, 404, Taiwan.
9
Division of Neurosurgical Oncology, Neurological Institute, Taichung Veterans General Hospital, Taichung, 407, Taiwan.
10
Institute of Medical Sciences, Tzu Chi University, Hualien, 970, Taiwan.
11
Department of Biotechnology, Asia University, Taichung, 413, Taiwan.

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.

KEYWORDS:

apoptosis; cell cycle arrest; crude extract of Rheum palmatum L. (CERP); human osteosarcoma cells U-2 OS

PMID:
25689151
DOI:
10.1002/tox.22105
[Indexed for MEDLINE]

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