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Targeted inhibition of the PI3K/AKT/mTOR pathway by (+)-anthrabenzoxocinone induces cell cycle arrest, apoptosis, and autophagy in non-small cell lung cancer

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机构： [1]The Third Affiliated Hospital of Zunyi Medical University, The First People's Hospital of Zunyi), Scientific Research Center, Guizhou, 563002, People's Republic of China. [2]Yunnan Characteristic Plant Extraction Laboratory, Key Laboratory of Medicinal Chemistry for Natural Resource, Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming, 650091, People's Republic of China.

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关键词： Anthrabenzoxocinones Non-small cell lung cancer Cell cycle arrest apoptosis Autophagy PI3K/AKT/mTOR pathway ROS

摘要：

Non-small cell lung cancer (NSCLC), characterized by low survival rates and a high recurrence rate, is a major cause of cancer-related mortality. Aberrant activation of the PI3K/AKT/mTOR signaling pathway is a common driver of NSCLC. Within this study, the inhibitory activity of (+)-anthrabenzoxocinone ((+)-ABX), an oxygenated anthrabenzoxocinone compound derived from Streptomyces, against NSCLC is demonstrated for the first time both in vitro and in vivo. Mechanistically, it is confirmed that the PI3K/AKT/mTOR signaling pathway is targeted and suppressed by (+)-ABX, resulting in the induction of S and G2/M phase arrest, apoptosis, and autophagy in NSCLC cells. Additionally, the augmentation of intracellular ROS levels by (+)-ABX is revealed, further contributing to the inhibition of the signaling pathway and exerting inhibitory effects on tumor growth. The findings presented in this study suggest that (+)-ABX possesses the potential to serve as a lead compound for the treatment of NSCLC.© 2024. The Author(s).

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大类 | 1 区生物学

小类 | 2 区生化与分子生物学 2 区细胞生物学

第一作者：

第一作者机构： [1]The Third Affiliated Hospital of Zunyi Medical University, The First People's Hospital of Zunyi), Scientific Research Center, Guizhou, 563002, People's Republic of China.

通讯作者：

通讯机构： [1]The Third Affiliated Hospital of Zunyi Medical University, The First People's Hospital of Zunyi), Scientific Research Center, Guizhou, 563002, People's Republic of China. [2]Yunnan Characteristic Plant Extraction Laboratory, Key Laboratory of Medicinal Chemistry for Natural Resource, Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming, 650091, People's Republic of China.

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Targeted inhibition of the PI3K/AKT/mTOR pathway by (+)-anthrabenzoxocinone induces cell cycle arrest, apoptosis, and autophagy in non-small cell lung cancer

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