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.

中文翻译：

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一种来自民族药用蘑菇的天然衍生物，通过微调人肺腺癌细胞 (A549) 中的 Akt 信号，增强细胞凋亡、自噬并减弱细胞迁移

近几十年来，虽然在晚期肺癌的综合治疗方面取得了广泛的成果，但临床上有效的抗肺癌治疗方法仍然不足。因此，非常需要引人注目的新型抗肺癌药物。这一背景促使我们揭示了野生食用蘑菇衍生物 astrakurkurol 的抗癌功效，其作用尚未被描述。机理分析表明，astrakurkurol 的致敏作用是由于细胞周期停滞在 G0/G1 期，Fas、FADD 水平增加，Bax/Bcl-2 比率降低，以及 caspase 9、8 和 3 的裂解形式增加。 除从诱导细胞凋亡，首次证明了 astrakurkurol 诱导了自噬反应，这可以通过酸性囊泡细胞器 (AVO) 的发展来证明，其中 beclin-1、Atg7 上调，p62 下调。细胞凋亡和自噬可以由相同的刺激引发，这从 astrakurkurol 诱导的 PI3K/AKT 信号失活可以明显看出。彻底扫描细胞凋亡和自噬之间的串扰机制是抗癌药物成功的必要条件。三萜类化合物对 A549 细胞具有明显增强的细胞毒性、诱导细胞凋亡和自噬作用。除了 astrakurkurol 还可以抑制迁移和缩小肿瘤的大小 这从 astrakurkurol 诱导的 PI3K/AKT 信号失活就很明显。彻底扫描细胞凋亡和自噬之间的串扰机制是抗癌药物成功的必要条件。三萜类化合物对 A549 细胞具有明显增强的细胞毒性、诱导细胞凋亡和自噬作用。除了 astrakurkurol 还可以抑制迁移和缩小肿瘤的大小 这从 astrakurkurol 诱导的 PI3K/AKT 信号失活就很明显。彻底扫描细胞凋亡和自噬之间的串扰机制是抗癌药物成功的必要条件。三萜类化合物对 A549 细胞具有明显增强的细胞毒性、诱导细胞凋亡和自噬作用。除了 astrakurkurol 还可以抑制迁移和缩小肿瘤的大小离体异种移植模型。所有这些发现都表明 astrakurkurol 是一种令人信服的新型抗癌剂，可用于审查肺癌疗法，并作为未来体外和体内分析的有力竞争者。