A natural derivative from ethnomedicinal mushroom potentiates apoptosis, autophagy and attenuates cell migration, via fine tuning the Akt signaling in human lung adenocarcinoma cells (A549)

自噬 细胞凋亡 PI3K/AKT/mTOR通路 蛋白激酶B 癌症研究 肺癌 A549电池 细胞生物学 化学 时尚 生物 医学 程序性细胞死亡 半胱氨酸蛋白酶 生物化学 内科学
作者
Sudeshna Nandi,Priyanka Upadhyay,Ayan Roy,Asish Dasgupta,Arnab Sen,Arghya Adhikary,Krishnendu Acharya
出处
期刊:Environmental Toxicology [Wiley]
卷期号:37 (1): 52-68 被引量:3
标识
DOI:10.1002/tox.23377
摘要

Although comprehensive exertions have been made in late decades for treating advanced lung cancer with inclusive therapies but efficient anti-lung cancer therapeutics are statically inadequate in the clinics. Hence, compelling novel anti-lung cancer drugs are considerably desired. This backdrop enticed us to unveil anticancer efficacy of astrakurkurol, derivative of wild edible mushroom against lung cancer, whose effects have not yet been described. Mechanistic analysis disclosed that sensitizing effect of astrakurkurol is due to cell cycle arrest at G0/G1 phase, increased level of Fas, FADD, decreased ratio of Bax/Bcl-2, and increased cleaved form of caspase 9, 8, and 3. Apart from the induction of apoptosis, it was demonstrated for the first time that astrakurkurol induced an autophagic response as evidenced by the development of acidic vesicular organelles (AVOs) with up-regulation of beclin-1, Atg7, and downregulated p62. Apoptosis and autophagy can be sparked by the same stimuli, which was as evident from the astrakurkurol-induced inactivation of PI3K/AKT signaling. The thorough scanning of the mechanism of crosstalk between apoptosis and autophagy is requisite for prosperous anticancer remedy. Triterpenoid has evidently intensified cytotoxicity, induced apoptosis and autophagy on A549 cells. Besides astrakurkurol could also curb migration and regress the size of tumor in ex ovo xenograft model. All these findings put forth astrakurkurol as a convincing novel anti-cancer agent, for scrutinizing the lung cancer therapies and as a robust contender for future in vitro and in vivo analysis.
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