San-Zhong-Kui-Jian-Tang, a Traditional Chinese Medicine Prescription, Inhibits the Proliferation of Human Breast Cancer Cell by Blocking Cell Cycle Progression and Inducing Apoptosis

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  • Hsu Ya-Ling
    Department of Pharmacy, Chia-Nan University of Pharmacy and Science
  • Yen Ming-Hong
    Faculty of Pharmacy, College of Pharmacy, Kaohsiung Medical University
  • Kuo Po-Lin
    Department of Biotechnology, Chia-Nan University of Pharmacy and Science
  • Cho Chien-Yu
    Graduate Institute of Natural Products, Kaohsiung Medical University
  • Huang Yu-Ting
    Department of Biotechnology, Chia-Nan University of Pharmacy and Science
  • Tseng Chien-Jung
    Graduate Institute of Natural Products, Kaohsiung Medical University
  • Lee Ju-Ping
    Department of Biotechnology, Chia-Nan University of Pharmacy and Science
  • Lin Chun-Ching
    Faculty of Pharmacy, College of Pharmacy, Kaohsiung Medical University

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Abstract

San-Zhong-Kui-Jian-Tang (SZKJT; Japanese name: Sanshu-kaigen-to), a traditional Chinese medicine prescription, has been used for treating patients with various cancers. This study first investigates the anticancer effect of SZKJT in two human breast cancer cell lines, MCF-7 and MDA-MB-231. SZKJT exhibited effective cell growth inhibition by inducing cancer cells to undergo G0/G1 phase arrest and apoptosis. Blockade of cell cycle was associated with increased p21/WAF1 levels, and reduced amounts of cyclinD1, cyclinD2 in a p53-independent manner. SZKJT treatment triggered the mitochondrial apoptotic pathway indicated by changing Bax/Bcl-2 ratios, cytochrome c release and caspase-9 activation, but did not act on Fas/Fas ligand pathways and the activation of caspase-8. Further investigation revealed that SZKJT's inhibition of cell growth effect was also evident in a nude mice model. Taken together, our study suggests that the induction of p21/WAF1 and activity of the mitochondrial apoptotic system may participate in the antiproliferative activity of SZKJY in human breast cancer cells.

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