Animal Tissue Culture and Molecular Genetics Laboratory, Department of Biotechnology, School of Biotechnology and Genetic Engineering, Bharathiar University, Coimbatore 641046, Tamilnadu, India.
Food Chem. 2013 Dec 15;141(4):3598-605. doi: 10.1016/j.foodchem.2013.05.138. Epub 2013 Jun 7.
Previously we have reported that neferine from the medicinal plant Nelumbo nucifera, inhibited cancer cell proliferation by inducing apoptosis. The present study was focused on the action mechanism of neferine in inducing autophagy in lung cancer cells. Neferine markedly inhibited A549 cell proliferation in a dose dependent manner. Acidic vesicular accumulation was observed in neferine treated cells as an indication of autophagy. Neferine could induce the conversion of LC3B-I to LC3B-II without affecting the expression levels of PI3KCIII and Beclin1. It has been observed that neferine mediated autophagy is dependent on inhibition of PI3K/Akt/mTOR signaling by neferine. Neferine treatment could also lead to the ROS hypergeneration and depletion of cellular antioxidant, GSH. The results demonstrate that neferine-induced autophagy is mediated through ROS hypergeneration and mTOR inhibition. Taken together, the present study unveils a novel mechanism of action of neferine on lung cancer cells in the induction of autophagy.
先前我们报道过，来自药用植物莲（Nelumbo nucifera）的小檗碱通过诱导细胞凋亡抑制癌细胞增殖。本研究集中于小檗碱在诱导肺癌细胞自噬中的作用机制。小檗碱呈剂量依赖性显著抑制 A549 细胞的增殖。在小檗碱处理的细胞中观察到酸性囊泡积累，这是自噬的一个迹象。小檗碱可以诱导 LC3B-I 向 LC3B-II 的转化，而不影响 PI3KCIII 和 Beclin1 的表达水平。已经观察到小檗碱介导的自噬依赖于小檗碱对 PI3K/Akt/mTOR 信号的抑制。小檗碱处理也可能导致 ROS 过度产生和细胞抗氧化剂 GSH 的耗竭。结果表明，小檗碱诱导的自噬是通过 ROS 过度产生和 mTOR 抑制介导的。综上所述，本研究揭示了小檗碱在诱导自噬中对肺癌细胞的作用的新机制。
