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J Cancer 2020; 11(15):4495-4509. doi:10.7150/jca.44383 This issue Cite

Research Paper

Cytoplasm-localized SIRT1 downregulation attenuates apoptosis and cell cycle arrest in cisplatin-resistant lung cancer A549 cells

Hyeran Yu1, Young Mee Kim1,✉, Moonjae Cho1,2,✉

1. Department of Biochemistry School of Medicine, Jeju National University, Jeju, Korea
2. Institutes of Medical Science, Jeju National University, Jeju, Korea

✉ Corresponding author: Moonjae Cho; E-mail: moonjchoac.kr, Tel.:+82-64-754-8117, Fax: +82-64-725-2593; Young Mee Kim; E-mail: biochem310ac.kr, Tel.:+82-64-754-8046, Fax: +82-64-725-2593

Citation:
Yu H, Kim YM, Cho M. Cytoplasm-localized SIRT1 downregulation attenuates apoptosis and cell cycle arrest in cisplatin-resistant lung cancer A549 cells. J Cancer 2020; 11(15):4495-4509. doi:10.7150/jca.44383. https://www.jcancer.org/v11p4495.htm
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Abstract

Objective: We propose that sirtuin (SIRT) may induce a pro-apoptotic effect by deacetylating transcription factors in A549 cells: depletion of sirtuin-1 (SIRT1) induced cell cycle arrest in cisplatin-resistant A549 (A549/CADD) cells.

Methods: Protein and mRNA levels of SIRT1 were investigated using western blot and RT-PCR. In A549 and A549/CADD cells, the cytotoxicity of cisplatin administration was evaluated by MTT assay, proliferation was measured by ECIS, and the cell cycle distribution was analyzed using FACS. Cells were transfected with pcDNA3.1-Myc-SIRT1 or pcDNA3.1-Myc-Control vectors to analyze the impact of SIRT-1 on cisplatin induced drug resistance. SIRT1 localization was studied using immunofluorescence analysis. In addition, immunoprecipitation and 20S proteasome activity assay were performed to examine the relationship of SIRT1 with the proteasome complex.

Results: A549/CADD cells exhibited a mesenchymal-like cell characteristic. SIRT1 expression was markedly decreased in A549/CADD cells. We observed that cisplatin regulates p53 stability through the depletion of ubiquitination following SIRT1 downregulation. Furthermore, cisplatin treatment increased proteasomal activity and significantly decreased cytoplasmic SIRT1 protein levels in A549/CADD cells.

Conclusion: In this study, we found SIRT1 to be depleted in A549/CADD cells and also determined the underlying resistance mechanism which may act as novel therapeutic targets in overcoming drug resistance.

Keywords: Cisplatin-resistant lung cancer, EMT, SIRT1, Cell cycle arrest, Apoptosis

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APA
Yu, H., Kim, Y.M., Cho, M. (2020). Cytoplasm-localized SIRT1 downregulation attenuates apoptosis and cell cycle arrest in cisplatin-resistant lung cancer A549 cells. Journal of Cancer, 11(15), 4495-4509. https://doi.org/10.7150/jca.44383.

ACS
Yu, H.; Kim, Y.M.; Cho, M. Cytoplasm-localized SIRT1 downregulation attenuates apoptosis and cell cycle arrest in cisplatin-resistant lung cancer A549 cells. J. Cancer 2020, 11 (15), 4495-4509. DOI: 10.7150/jca.44383.

NLM
Yu H, Kim YM, Cho M. Cytoplasm-localized SIRT1 downregulation attenuates apoptosis and cell cycle arrest in cisplatin-resistant lung cancer A549 cells. J Cancer 2020; 11(15):4495-4509. doi:10.7150/jca.44383. https://www.jcancer.org/v11p4495.htm

CSE
Yu H, Kim YM, Cho M. 2020. Cytoplasm-localized SIRT1 downregulation attenuates apoptosis and cell cycle arrest in cisplatin-resistant lung cancer A549 cells. J Cancer. 11(15):4495-4509.

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