Telmisartan-Induced Cytotoxicity via G2/M Phase Arrest in Renal Cell Carcinoma Cell Lines

• Published in: Biological & pharmaceutical bulletin 2021/12/01, Vol.44(12), pp.1878-1885
• Main Authors: Tsujiya, Yoshie, Hasegawa, Ai, Yamamori, Motohiro, Okamura, Noboru
• Format: Article
• Language: English
• Subjects: AKT protein; angiotensin II receptor blocker; Antitumor activity; Apoptosis; Bax protein; Bcl-2 protein; c-Jun protein; Cell cycle; cell cycle arrest; Cell death; Cell migration; Cell viability; Chromatin; Cytotoxicity; Extracellular signal-regulated kinase; Flow cytometry; JNK protein; Kidney cancer; Phosphorylation; Rapamycin; Renal cell carcinoma; telmisartan; TOR protein; Transcription factors; Tumor cell lines; Western blotting
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b21-00654

Renal cell carcinoma (RCC) is the most common type of kidney cancer. Given that stage IV RCC is intractable, there is a need for a novel treatment strategy. We investigated the antitumor effects of telmisartan (TEL) and their underlying mechanisms in RCC, including their impact on apoptosis, Akt/mammalian target of rapamycin (mTOR) pathways, and the cell cycle using two human RCC cell lines: 786-O and Caki-2. Cell viability was detected via fluorescence-based assays. Cells were stained with Hoechst 33342 to observe chromatin condensation, and Western blotting was performed to analyze protein expression. The cell cycle was assessed using flow cytometry. Invasion and migration assays were performed using 24-well chambers. TEL induced cell death in a dose-dependent manner and increased the percentage of cells with high chromatin condensation and Bax/Bcl-2 ratio in both cell lines. TEL-induced cell death was attenuated by neither peroxisome proliferator-activated receptor-γ nor -δ inhibitors. Although TEL elevated c-Jun N-terminal kinase levels and p38 phosphorylation rates in Caki-2 cells, as well as extracellular signal-regulated kinase phosphorylation rates in 786-O cells, their inhibitors did not suppress TEL-induced cell death. TEL decreased Akt phosphorylation in 786-O cells and mTOR phosphorylation in both cell lines, increased the population of cells in the G2/M phase, and altered G2/M-related proteins in both cell lines. TEL moderately suppressed cell invasion and migration in 786-O and Caki-2 cells, respectively, and increased cell invasion in Caki-2 cells, suggesting a potential therapeutic role of TEL in RCC.