Licochalcone A induces autophagy through PI3K/Akt/mTOR inactivation and autophagy suppression enhances Licochalcone A-induced apoptosis of human cervical cancer cells.
Licochalcone A induces autophagy through PI3K/Akt/mTOR inactivation and autophagy suppression enhances Licochalcone A-induced apoptosis of human cervical cancer cells.
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DOI：
10.18632/oncotarget.4767
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发表时间：
2015-10-06
期刊：
影响因子：
--
通讯作者：
Hsieh YH
中科院分区：
文献类型：
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作者：
Tsai JP;Lee CH;Ying TH;Lin CL;Lin CL;Hsueh JT;Hsieh YH
在化学预防中使用膳食生物活性化合物可以潜在地逆转、抑制甚至阻止癌症的进展。然而，LicA对宫颈癌细胞凋亡和自噬的影响尚不清楚。本研究发现，LicA处理在体外和体内均能显著诱导宫颈癌细胞的凋亡和自噬能力。MTT试验结果显示，LicA对4种宫颈癌细胞系具有剂量依赖性和时间依赖性的细胞毒性。我们发现LicA诱导SiHa细胞线粒体依赖性凋亡，降低Bcl-2表达。通过鉴定Atg5、Atg7、Atg12和微管相关蛋白1轻链3 (LC3)-II的积累，研究了LicA诱导的自噬效应。自噬特异性抑制剂（3-甲基腺嘌呤和巴菲霉素A1）增强了lica诱导的细胞凋亡。此外，我们提出LicA可抑制磷脂酰肌醇3-激酶(PI3K)/Akt/ mTOR通路的哺乳动物靶点。此外，LY294002/si-Akt抑制PI3K/Akt或雷帕霉素抑制mTOR增强了lica诱导的细胞凋亡和自噬。最后，在SiHa异种移植小鼠体内，LicA剂量为10或20 mg/kg显著抑制肿瘤生长。我们的研究结果证明了LicA治疗人类宫颈癌的化疗潜力。
The use of dietary bioactive compounds in chemoprevention can potentially reverse, suppress, or even prevent cancer progression. However, the effects of licochalcone A (LicA) on apoptosis and autophagy in cervical cancer cells have not yet been clearly elucidated. In this study, LicA treatment was found to significantly induce the apoptotic and autophagic capacities of cervical cancer cells in vitro and in vivo. MTT assay results showed dose- and time-dependent cytotoxicity in four cervical cancer cell lines treated with LicA. We found that LicA induced mitochondria-dependent apoptosis in SiHa cells, with decreasing Bcl-2 expression. LicA also induced autophagy effects were examined by identifying accumulation of Atg5, Atg7, Atg12 and microtubule-associated protein 1 light chain 3 (LC3)-II. Treatment with autophagy-specific inhibitors (3-methyladenine and bafilomycin A1) enhanced LicA-induced apoptosis. In addition, we suggested the inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of mTOR pathway by LicA. Furthermore, the inhibition of PI3K/Akt by LY294002/si-Akt or of mTOR by rapamycin augmented LicA-induced apoptosis and autophagy. Finally, the in vivo mice bearing a SiHa xenograft, LicA dosed at 10 or 20 mg/kg significantly inhibited tumor growth. Our findings demonstrate the chemotherapeutic potential of LicA for treatment of human cervical cancer.