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.

Synthesis, characterization, crystal structure, thermal and redox behaviour and antiproliferative studies of morpholine‐based two copper(II) compounds

“…In vitro assessment has already displayed that the compound has potent antiproliferative activity against A549 cells. Further inhibition of proliferation was examined by measuring cell cycle distribution using PI stain following treatment with different concentrations of 1 and 2 for 24 h as per the standardized protocol of Nandi and co‐workers 39 . The DNA content of A549 cells in different phases of cell cycle was investigated.…”

“…Further inhibition of proliferation was examined by measuring cell cycle distribution using PI stain following treatment with different concentrations of 1 and 2 for 24 h as per the standardized protocol of Nandi and co-workers. 39 The DNA content of A549 cells in different phases of cell cycle was investigated. The histograms from flow cytometer demonstrated an increase in cell population at the sub-G0 phase with concomitant decrease in the proportion of cells in the G0/G1, S and G2/M phases of the cell cycle of treated cells in both the compounds when compared with the untreated control cells.…”

EPN3 plays oncogenic role in non‐small cell lung cancer by activating the JAK1/2‐STAT3 pathway

“…However, its treatment remains a grim challenge 22–25 . Elucidation of the mechanisms of NSCLC development will help develop effective treatment strategies 26–31 . This study deciphered the exact function of EPN3 in NSCLC.…”

“…[22][23][24][25] Elucidation of the mechanisms of NSCLC development will help develop effective treatment strategies. [26][27][28][29][30][31] This study deciphered the exact function of EPN3 in NSCLC. The results indicated that EPN3 was aberrantly over-modulated in NSCLC patients and cells.…”

Design, synthesis and structure of a trinuclear copper(ii) complex having a Cu3OH core with regard to aspects of antiproliferative activity and magnetic properties

“…The in vitro scratch wound repair assay was a modification of a previously described methodology of Nandi et al 30 Briefly, 5 × 10 4 A549 cells per mL were cultured in 6-well plates to confluence as monolayers under standard conditions. Upon reaching a confluence of more than 75% for cultured cells, linear wounds were made with a 100 μL pipette tip on cell monolayers followed by incubation with serum-free conditioned media for 24 h. Circumferential wound gaps were measured by ImageJ software and the percentage of wound repair was calculated.…”