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).

Abstract

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.