自噬
安普克
细胞凋亡
PI3K/AKT/mTOR通路
黑色素瘤
细胞周期
癌症研究
细胞生物学
化学
蛋白激酶B
细胞生长
细胞周期检查点
癌细胞
生物
蛋白激酶A
激酶
癌症
生物化学
遗传学
作者
Xiaoting Wang,Xiaojie Li,Xiaocong Yuan,Danyang Wang,Xiaohan Li,Ling Liu,Qin Zheng,Defang Li,Qingling Jiang
标识
DOI:10.1021/acs.jnatprod.2c00098
摘要
Hernandezine is isolated from an herbal medicine that selectively inhibits multidrug resistance and improves the efficacy of drugs for cancer treatment. To date, no studies on hernandezine in melanoma have been conducted. In this study, hernandezine was found to inhibit proliferation and induce apoptosis in melanoma A375 cells and B16 cells. In hernandezine-treated melanoma cells, G0/G1 cycle arrest occurred accompanied by significantly downregulated levels of phosphorylated JAK2 and STAT3. In addition, the cycle arrest could be enhanced by AG490 (JAK2 inhibitor), suggesting that the JAK2/STAT3 pathway is involved in cell cycle regulation in hernandezine-treated melanoma cells. Hernandezine-treated melanoma cells exhibited autophagy-specific structures, autophagy markers (LC3II/LC3-I), and autophagic flow over time. Moreover, 3-MA (autophagy inhibitor) significantly inhibited apoptosis, indicating that hernandezine promotes apoptosis by inducing autophagy. Combined with differential expression of P-AMPK, P-ACC (downstream targets of adenine monophosphate activated protein kinase, AMPK), and P-p70S6K (downstream targets of mammalian target of rapamycin, mTOR) and significant inhibition of apoptosis by AMPK inhibitor complex C (CC) in hernandezine-treated melanoma cells suggested that hernandezine could induce autophagy via the AMPK-mTOR pathway, thereby inducing apoptosis. This study first analyzed the effect of melanoma cells by hernandezine and provided a theory for hernandezine in the treatment of melanoma.
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