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The Anthraquinone Derivative C2 Enhances Oxaliplatin-Induced Cell Death and Triggers Autophagy via the PI3K/AKT/mTOR Pathway.

Authors :
Li, Yuying
Yan, Wei
Qin, Yu
Zhang, Liwei
Xiao, Sheng
Source :
International Journal of Molecular Sciences; Jun2024, Vol. 25 Issue 12, p6468, 15p
Publication Year :
2024

Abstract

Chemotherapy resistance in cancer is an essential factor leading to high mortality rates. Tumor multidrug resistance arises as a result of the autophagy process. Our previous study found that compound 1-nitro-2 acyl anthraquinone-leucine (C2) exhibited excellent anti-colorectal cancer (CRC) activity involving autophagy and apoptosis-related proteins, whereas its underlying mechanism remains unclear. A notable aspect of this study is how C2 overcomes the multidrug susceptibility of HCT116/L-OHP, a colon cancer cell line that is resistant to both in vitro and in vivo oxaliplatin (trans-/-diaminocyclohexane oxalatoplatinum; L-OHP). In a xenograft tumor mouse model, we discovered that the mixture of C2 and L-OHP reversed the resistance of HCT116/L-OHP cells to L-OHP and inhibited tumor growth; furthermore, C2 down-regulated the gene expression levels of P-gp and BCRP and decreased P-gp's drug efflux activity. It is important to note that while C2 re-sensitized the HCT116/L-OHP cells to L-OHP for apoptosis, it also triggered a protective autophagic pathway. The expression levels of cleaved caspase-3 and Beclin 1 steadily rose. Expression of PI3K, phosphorylated AKT, and mTOR were decreased, while p53 increased. We demonstrated that the anthraquinone derivative C2 acts as an L-OHP sensitizer and reverses resistance to L-OHP in HCT116/L-OHP cells. It suggests that C2 can induce autophagy in HCT116/L-OHP cells by mediating p53 and the PI3K/AKT/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
16616596
Volume :
25
Issue :
12
Database :
Complementary Index
Journal :
International Journal of Molecular Sciences
Publication Type :
Academic Journal
Accession number :
178185896
Full Text :
https://doi.org/10.3390/ijms25126468