Gypenoside L Inhibits Proliferation of Liver and Esophageal Cancer Cells by Inducing Senescence
Gypenoside L Inhibits Proliferation of Liver and Esophageal Cancer Cells by Inducing Senescence
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绞股蓝皂苷 L 通过诱导衰老抑制肝癌和食道癌细胞的增殖
DOI：
10.3390/molecules24061054
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发表时间：
2019-03-02
期刊：
影响因子：
4.6
通讯作者：
Zheng, Kai
中科院分区：
文献类型：
--
作者：
Ma, Jingxin;Hu, Xiaopeng;Zheng, Kai
衰老是细胞周期停滞的不可逆状态，可由多种刺激（如氧反应性物质和DNA损伤）触发。越来越多的证据已经证明衰老是癌症治疗中的肿瘤抑制方法。因此，开发调节衰老的新药物可能是对抗癌症的替代策略。在我们的研究中，我们研究了绞股蓝皂苷L（Gypenoside L，Gyp-L）对癌细胞生长的抑制作用。结果表明，Gyp-L可提高SA-β-半乳糖苷酶活性，促进衰老相关分泌性细胞因子的产生，抑制人肝癌和食管癌细胞的增殖。此外，Gyp-L引起细胞周期停滞在S期，并激活衰老相关的细胞周期抑制蛋白（p21和p27）及其上游调控因子。此外，Gyp-L还通过激活p38、ERK MAPK通路和NF-κB通路诱导衰老。因此，添加化学抑制剂有效地抵消了Gyp-L介导的癌细胞衰老、生长抑制和细胞周期停滞。此外，Gyp-L处理增强了临床治疗药物，包括5-氟尿嘧啶和顺铂对癌细胞的细胞毒性。总的来说，这些结果表明Gyp-L通过诱导衰老抑制癌细胞的增殖，并使癌细胞对化疗更敏感。
Senescence is an irreversible state of cell cycle arrest that can be triggered by multiple stimuli, such as oxygen reactive species and DNA damage. Growing evidence has proven that senescence is a tumor-suppressive approach in cancer treatment. Therefore, developing novel agents that modulate senescence may be an alternative strategy against cancer. In our study, we investigated the inhibitory effect of gypenoside L (Gyp-L), a saponin isolated from Gynostemma pentaphyllum, on cancer cell growth. We found that Gyp-L increased the SA-β-galactosidase activity, promoted the production of senescence-associated secretory cytokines, and inhibited cell proliferation of human liver and esophageal cancer cells. Moreover, Gyp-L caused cell cycle arrest at S phase, and activated senescence-related cell cycle inhibitor proteins (p21 and p27) and their upstream regulators. In addition, Gyp-L activated p38 and ERK MAPK pathways and NF-κB pathway to induce senescence. Consistently, adding chemical inhibitors efficiently counteracted the Gyp-L-mediated senescence, growth inhibition, and cell cycle arrest in cancer cells. Furthermore, treatment with Gyp-L, enhanced the cytotoxicity of clinic therapeutic drugs, including 5-fluorouracil and cisplatin, on cancer cells. Overall, these results indicate that Gyp-L inhibits proliferation of cancer cells by inducing senescence and renders cancer cells more sensitive to chemotherapy.