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The Mechanisms of Chansu in Inducing Efficient Apoptosis in Colon Cancer Cells

机译:蟾酥诱导结肠癌细胞高效凋亡的机制

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摘要

Chansu is one of the most widely used traditional Chinese medicines in China, Japan, and other Southeast Asian countries primarily for antipain, anti-inflammation, and recently anticancer. Over 10 recipes and remedies contained Chansu, which are easily available in pharmacies and hospitals, but the mechanisms of action were not clearly articulated. In the present study, Cinobufagin (CBF), the major compound of Chansu, was employed as a surrogate marker to determine its ability in inducing cancer cell death. As expected, CBF has significant cancer-killing capacity for a range of cancers, but such ability differs markedly. Colon and prostate cancers are more sensitive than skin and lung cancers. Interestingly, cancer cells die through apoptotic pathway either being biphasic caspase-3-dependent (HCT116) or independent (HT29). Multipathway analysis reveals that CBF-induced apoptosis is likely modulated by the hypoxia-inducing factor-1 alpha subunit (HIF-1α) as its inhibition was evident in vitro and in vivo. Taken together, these results demonstrate that CBF is a potent apoptotic inducer with potential for further development as a novel and effective anticancer agent for a range of cancers, especially colon cancer.
机译:在中国,日本和其他东南亚国家,Chansu是最广泛使用的中药之一,主要用于止痛,抗炎和抗癌。 Chansu包含10多种食谱和疗法,可在药房和医院轻松获得,但作用机理尚未明确阐明。在本研究中,Chanbufagin(CBF),Chansu的主要化合物,被用作替代标记,以确定其诱导癌细胞死亡的能力。不出所料,CBF对多种癌症具有显着的杀癌能力,但这种能力明显不同。结肠癌和前列腺癌比皮肤癌和肺癌更敏感。有趣的是,癌细胞通过凋亡途径而死亡,该凋亡途径是双相的caspase-3依赖性(HCT116)或非依赖性(HT29)。多途径分析显示,CBF诱导的凋亡可能受缺氧诱导因子1α亚基(HIF-1α)的调节,因为其在体内和体外均有明显的抑制作用。综上所述,这些结果表明,CBF作为一种有效的凋亡诱导剂,有可能作为新型且有效的抗癌剂用于多种癌症(尤其是结肠癌)的进一步开发。

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