Paris saponin II of Rhizoma Paridis - A novel inducer of apoptosis in human ovarian cancer cells
Paris saponin II of Rhizoma Paridis - A novel inducer of apoptosis in human ovarian cancer cells
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DOI：
10.5582/bst.2012.v6.4.201
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发表时间：
2012-01-01
影响因子：
5.5
通讯作者：
Wang, He
中科院分区：
文献类型：
--
作者：
Xiao, Xue;Zou, Juan;Wang, He
麦冬（Rhizoma Paraphylaxis）是传统中草药的重要成分。近十年来，重楼的活性成分--巴黎皂苷已成为一种很有前途的抗癌药物。在这些皂苷中，多叶皂苷D（巴黎皂苷（PS）I）已被广泛研究并被认为是有效的抗肿瘤剂。在这项研究中，我们继续建立的疗效和机制的类固醇PS成员的细胞毒性作用，即台湾山奈C（PSII）在卵巢癌治疗。我们分离PSII，并评估其对一组10个人类细胞系的影响。分离的PSII对肿瘤细胞的生长具有有效的抑制作用，而对不同的正常细胞类型或良性肿瘤衍生细胞没有有害作用。虽然PSII、PSI和依托泊苷是细胞周期停滞和凋亡的有效促进剂，但PSII似乎在抑制SKOV 3细胞生长方面比后两者稍微更有效。在PSII处理的SKOV 3细胞中，促凋亡元素，包括Bax，胞浆细胞色素c，活化的caspase-3和活化的caspase-9升高。治疗还减少了细胞外信号调节激酶（ERK 1/2）磷酸化和抗凋亡Bcl-2的表达。我们还评估了腹膜内施用PSII在无胸腺小鼠中的人SKOV 3卵巢癌异种移植物中的抗肿瘤功效。PSII处理相对于对照显著抑制异种移植肿瘤的生长达70%（p < 0.05）。这些发现表明，除了对癌细胞的独特选择性之外，PSII是一种有效的抗肿瘤分子，可以开发为癌症治疗剂。
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.