Paris saponin II of Rhizoma Paridis – A novel inducer of apoptosis in human ovarian cancer cells

  • Xiao Xue
    Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University Department of Pathology, The University of Texas M. D. Anderson Cancer Center
  • Zou Juan
    Department of Pathology, West China Second University Hospital, Sichuan University
  • Minh Bui-Nguyen Tri
    Department of Biochemistry and Molecular Biology, The George Washington University
  • Bai Peng
    West China School of Preclinical and Forensic Medicine, Sichuan University
  • Gao Linbo
    Laboratory of Molecular and Translational Medicine, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University
  • Liu Jinsong
    Department of Pathology, The University of Texas M. D. Anderson Cancer Center
  • Liu Shanling
    Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University
  • Xiao Jianguo
    Department of Pathology, The University of Texas M. D. Anderson Cancer Center
  • Chen Xinlian
    Lab of Genetics, West China Second University Hospital, Sichuan University
  • Zhang Xuemei
    Lab of Genetics, West China Second University Hospital, Sichuan University
  • Wang He
    Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University

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Description

Rhizoma Paridis (dried root and rhizome) has been an essential ingredient in traditional Chinese herbal medicine. In the past decade, active components of Rhizoma Paridis ‒ the Paris saponins have emerged as promising anti-cancer agents. Among these saponins, polyphyllin D (Paris saponin (PS) I), has been extensively studied and proposed to be a potent antitumor agent. In this study, we continue to establish the efficacy and mechanisms underlying the cytotoxic effects of the steroidal PS members, namely formosanin C (PSII) in ovarian cancer treatment. We isolated PSII and evaluated its effects on a panel of ten human cell lines. Isolated PSII has potent inhibitory effects on the growth of tumor cells without deleterious effects to different normal cell types or benign neoplastic derived cells. While PSII, PSI, and etoposide are effective promoting agents for cell cycle arrest and apoptosis, PSII appeared to be marginally more potent than the later two in inhibiting SKOV3 cell growth. In PSII-treated SKOV3 cells, there was an elevation in proapoptotic elements including Bax, cytosolic cytochrome c, activated-caspase-3, and activated-caspase-9. The treatment also reduced extracellular signal-regulated kinase (ERK1/2) phosphorylation and anti-apoptotic Bcl-2 expression. We also assessed the antitumor efficacy of intraperitoneal administration of PSII in human SKOV3 ovarian cancer xenografts in athymic mice. PSII treatment significantly inhibited the growth of xenograft tumors relative to controls by 70% (p < 0.05). These findings demonstrated that, in addition to the unique selectivity against cancer cells, PSII is a potent antitumor molecule that may be developed as a cancer therapeutic agent.

Journal

  • BioScience Trends

    BioScience Trends 6 (4), 201-211, 2012

    International Research and Cooperation Association for Bio & Socio-Sciences Advancement

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