Crude extract of R heum palmatum L. Induces cell cycle arrest S phase and apoptosis through mitochondrial‐dependent pathways in U‐2 OS human osteosarcoma cells

作者：Chin‐Chung Lin, Ming‐Huei Lee, Ju‐Hwa Lin, Meng‐Liang Lin, Fu‐Shin Chueh, Chien‐Chih Yu, Jing‐Pin Lin, Yu‐Cheng Chou, Shu‐Chun Hsu, Jing‐Gung Chung · 发表于：Environmental Toxicology · 年份：2015 · DOI：10.1002/tox.22105 · 被引用次数：13 · 研究领域：Cell death mechanisms and regulation、Phytochemistry and biological activity of medicinal plants、Cancer-related Molecular Pathways

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.