Mechanism of action of alkaloids in Fritillaria-induced autophagy and apoptosis in non-small cell lung cancer

贝母类生物碱在非小细胞肺癌中诱导自噬和细胞凋亡的作用机制

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Abstract

The medicinal plant, Fritillaria (commonly known as beimu), exerts notable therapeutic effects on respiratory tract and lung diseases. Its active alkaloid components have exhibited efficacy against non-small cell lung cancer (NSCLC). The present study screened the anti-NSCLC protein targets of alkaloids in Fritillaria and validated their functional activity in vitro. Network pharmacology analysis indicated that alkaloids with activity against NSCLC target >300 proteins. Verticinone and ebeiedinone inhibited the proliferation of A549 and H1299 cells. After treating H1299 and A549 cells with 15 µM verticinone, the cell survival rate dropped to 75.57±4.80% and 68.9±3.06%, respectively. After treating both cell lines with 15 µM ebeiedinone, the cell survival rates dropped to 65.75±6.44% and 67±3.20%, respectively. At 30 µM, ebeiedinone could induce 26.44% of the cells to undergo apoptosis, which collectively indicates that the two compounds have anti-proliferative and induction of apoptosis effects on NSCLC cells. Additionally, the expression of LC3-II induced by ebeiedinone (30 µM) was significantly increased in the presence of the autophagy inhibitor, chloroquine, suggesting an enhancement of the autophagic flux. In summary, the findings of the present study demonstrated the significant inhibitory effect of Fritillaria alkaloids on NSCLC, which was closely associated with increased apoptosis and autophagy.

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