Laboratory of Urology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, China. *Contributed equally.
✉ Corresponding authors: Dr Xiaojun Chen, Laboratory of Urology, Affiliated Hospital of Guangdong Medical University, 57 Renmin Street South, Zhanjiang, Guangdong 524001, China. Email: 13170299com; Dr Jianjun Liu, Laboratory of Urology, Affiliated Hospital of Guangdong Medical University, 57 Renmin Street South, Zhanjiang, Guangdong 524001, China. Email: jianjunliulabcom.More
Citation:
Zhao Y, Lin S, Zeng W, Lin X, Qin X, Miu B, Gao S, Wu H, Liu J, Chen X. JS-K activates G2/M checkpoints through the DNA damage response and induces autophagy via CAMKKβ/AMPKα/mTOR pathway in bladder cancer cells. J Cancer 2024; 15(2):343-355. doi:10.7150/jca.86393. https://www.jcancer.org/v15p0343.htm
The aim of this study was to investigate the effects of JS-K, a nitric oxide donor prodrug, on DNA damage and autophagy in bladder cancer (BCa) cells and to explore the potential related mechanisms. Through detecting proliferation viability, cell morphology observation and colony formation assay low concentrations of JS-K significantly inhibited BCa growth while having no effect on normal cells. JS-K induced an increase in the level of DNA damage protein γH2AX and a decrease in the level of DNA damage repair-related proteins PCNA and RAD51 in BCa cells, indicating that JS-K can induce DNA damage in BCa cells and inhibit DNA damage repair. JS-K induced G2/M phase block and calcium overload using flow cytometry analysis. Moreover, we also investigated the levels of cell G2/M cycle checkpoint-related protein and autophagy-associated protein by western blot. The results of our study demonstrated that JS-K induced BCa cells G2/M phase arrest due to upregulating proteins related to DNA damage-related G2/M checkpoint activation (p-ATM, p-ATR, p-Chk1, p-Chk2, and p-Cdc2) and down-regulation of Cyclin B1 protein. In addition, our study demonstrated that JS-K-induced autophagy in BCa cells was related to the CAMKKβ/AMPKα/mTOR pathway.
Keywords: Bladder cancer, NO prodrug, DNA damage, Cell arrest, Autophagy
Citation styles
APA
Zhao, Y., Lin, S., Zeng, W., Lin, X., Qin, X., Miu, B., Gao, S., Wu, H., Liu, J., Chen, X. (2024). JS-K activates G2/M checkpoints through the DNA damage response and induces autophagy via CAMKKβ/AMPKα/mTOR pathway in bladder cancer cells. Journal of Cancer, 15(2), 343-355. https://doi.org/10.7150/jca.86393.
ACS
Zhao, Y.; Lin, S.; Zeng, W.; Lin, X.; Qin, X.; Miu, B.; Gao, S.; Wu, H.; Liu, J.; Chen, X. JS-K activates G2/M checkpoints through the DNA damage response and induces autophagy via CAMKKβ/AMPKα/mTOR pathway in bladder cancer cells. J. Cancer 2024, 15 (2), 343-355. DOI: 10.7150/jca.86393.
NLM
Zhao Y, Lin S, Zeng W, Lin X, Qin X, Miu B, Gao S, Wu H, Liu J, Chen X. JS-K activates G2/M checkpoints through the DNA damage response and induces autophagy via CAMKKβ/AMPKα/mTOR pathway in bladder cancer cells. J Cancer 2024; 15(2):343-355. doi:10.7150/jca.86393. https://www.jcancer.org/v15p0343.htm
CSE
Zhao Y, Lin S, Zeng W, Lin X, Qin X, Miu B, Gao S, Wu H, Liu J, Chen X. 2024. JS-K activates G2/M checkpoints through the DNA damage response and induces autophagy via CAMKKβ/AMPKα/mTOR pathway in bladder cancer cells. J Cancer. 15(2):343-355.
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