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
; 29(1): 58, 2024 Apr 23.
Article
in En
| MEDLINE
| ID: mdl-38649803
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Autophagy
/
Signal Transduction
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Apoptosis
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Carcinoma, Non-Small-Cell Lung
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Phosphatidylinositol 3-Kinases
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Proto-Oncogene Proteins c-akt
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TOR Serine-Threonine Kinases
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Cell Cycle Checkpoints
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Lung Neoplasms
Limits:
Animals
/
Humans
Language:
En
Journal:
Cell Mol Biol Lett
Journal subject:
BIOLOGIA MOLECULAR
Year:
2024
Type:
Article