Paris Polyphylla Inhibits Colorectal Cancer Cells via Inducing Autophagy and Enhancing the Efficacy of Chemotherapeutic Drug Doxorubicin

Paris Polyphylla Inhibits Colorectal Cancer Cells via Inducing Autophagy and Enhancing the Efficacy of Chemotherapeutic Drug Doxorubicin
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DOI:
10.3390/molecules24112102
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发表时间:
2019-06-01
期刊:
影响因子:
4.6
通讯作者:
Tai, Chen-Jei
Tai, Chen-Jei
中科院分区:
化学2区
文献类型:
--
作者:
Lin, Liang-Tzung;Uen, Wu-Ching;Tai, Chen-Jei

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结直肠癌是世界上最常见的癌症之一,化疗是治疗晚期和复发病例的主要方法。开发一种有效的补充疗法有助于提高肿瘤抑制效率和控制化疗的不良反应。巴黎是一种治疗各种癌症的民间药物,但其对结直肠癌的作用在很大程度上未被探索。本研究的目的是探讨从P. polyphylla乙醇提取物(EEPP)在DLD-1人大肠癌细胞的肿瘤抑制效果和作用机制,并评估其与化疗药物阿霉素的联合作用。数据表明EEPP通过上调自噬标志物诱导DLD-1细胞死亡,而不触发p53和caspase-3依赖性凋亡。此外,EEPP治疗与阿霉素的组合增强了这些肿瘤细胞的细胞毒性。从EEPP中分离得到偏诺皂苷元3-O-β-chacotrioside和polyphyllin VI,并鉴定为主要的候选活性成分。我们的研究结果表明,EEPP值得进一步评价发展为补充化疗结直肠癌。
Colorectal cancer is one of the most common cancers worldwide and chemotherapy is the main approach for the treatment of advanced and recurrent cases. Developing an effective complementary therapy could help to improve tumor suppression efficiency and control adverse effects from chemotherapy. Paris polyphylla is a folk medicine for treating various forms of cancer, but its effect on colorectal cancer is largely unexplored. The aim of the present study is to investigate the tumor suppression efficacy and the mechanism of action of the ethanolic extract from P. polyphylla (EEPP) in DLD-1 human colorectal carcinoma cells and to evaluate its combined effect with chemotherapeutic drug doxorubicin. The data indicated that EEPP induced DLD-1 cell death via the upregulation of the autophagy markers, without triggering p53- and caspase-3-dependent apoptosis. Moreover, EEPP treatment in combination with doxorubicin enhanced cytotoxicity in these tumor cells. Pennogenin 3-O-beta-chacotrioside and polyphyllin VI were isolated from EEPP and identified as the main candidate active components. Our results suggest that EEPP deserves further evaluation for development as complementary chemotherapy for colorectal cancer.