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

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

  • Cell Mol Biol Lett. 2024 Apr 23;29(1):58. doi: 10.1186/s11658-024-00578-6.
Xiao-Qian Li 1,  Xiao-Ju Cheng 1,  Jie Wu 1,  Kai-Feng Wu 2,  Tie Liu 3 4
Affiliations

Affiliations

  • 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 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. kiphoonwu@126.com.
  • 3 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. liutiefes@outlook.com.
  • 4 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. liutiefes@outlook.com.
PMID: 38649803 DOI: 10.1186/s11658-024-00578-6
Abstract

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.

Keywords

Anthrabenzoxocinones; Autophagy; Cell cycle arrest apoptosis; Non-small cell lung cancer; PI3K/AKT/mTOR pathway; ROS.

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