Department of Pharmacy, Zaozhuang Mental Health Center, Zaozhuang, 277103, China.
Department of Pharmacy, Zaozhuang Municipal Hospital, No.41 of Longtou Middle Road, Shizhong District, Zaozhuang, 277100, China.
Biomed Pharmacother. 2018 Jul;103:699-707. doi: 10.1016/j.biopha.2018.04.072. Epub 2018 Apr 24.
Apigenin is a dietary flavonoid with known antioxidant and antitumor effects against several types of cancers by promoting cell death and inducing cell cycle arrest. Apigenin also regulates a variety of intracellular signal transduction pathways during apoptosis or autophagy. However, the precise mechanism underlying the anticancer effects of apigenin in liver cancer remains poorly understood. In this study, we demonstrated that apigenin has anticancer activity against hepatocellular carcinoma cells. Apigenin inhibited the cell growth and induced cell death in a dose- and time-dependent manner in HepG2 cells. We found that apigenin treatment increased the expression of LC3-II and the number of GFP-LC3 puncta. Moreover, inhibition of autophagy with 3-MA and Atg5 gene silencing strengthened apigenin-induced proliferation inhibition and apoptosis. Our data has indicated that apigenin-induced autophagy has a protective effect against cell death. Additionally, apigenin induced apoptosis and autophagy through inhibition of PI3K/Akt/mTOR pathway. Most importantly, in vivo data showed that administration of apigenin decreased tumor growth and autophagy inhibition by 3-MA significantly enhanced the anticancer effect of apigenin. Collectively, our results reveal that apigenin inhibits cell proliferation and induces autophagy via suppressing the PI3K/Akt/mTOR pathway. Our results also suggest combination of autophagy inhibitors and apigenin would be a potential chemotherapeutic strategy against hepatocellular carcinoma.
芹菜素是一种膳食类黄酮，具有已知的抗氧化和抗肿瘤作用，可通过促进细胞死亡和诱导细胞周期停滞来抵抗多种类型的癌症。芹菜素还可在细胞凋亡或自噬过程中调节多种细胞内信号转导途径。然而，芹菜素在肝癌中的抗癌作用的确切机制仍知之甚少。在这项研究中，我们证明了芹菜素有抗肝癌活性。芹菜素以剂量和时间依赖的方式抑制 HepG2 细胞的细胞生长并诱导细胞死亡。我们发现，芹菜素处理增加了 LC3-II 的表达和 GFP-LC3 斑点的数量。此外，用 3-MA 抑制自噬和 Atg5 基因沉默增强了芹菜素诱导的增殖抑制和细胞凋亡。我们的数据表明，芹菜素诱导的自噬对细胞死亡具有保护作用。此外，芹菜素通过抑制 PI3K/Akt/mTOR 通路诱导细胞凋亡和自噬。最重要的是，体内数据表明，给予芹菜素可降低肿瘤生长，而 3-MA 抑制自噬则可显著增强芹菜素的抗癌作用。总之，我们的研究结果表明，芹菜素通过抑制 PI3K/Akt/mTOR 通路抑制细胞增殖并诱导自噬。我们的研究结果还表明，自噬抑制剂与芹菜素联合使用可能是治疗肝癌的一种潜在化疗策略。
