Sodium arsenite and dimethylarsenic acid induces apoptosis in OC3 oral cavity cancer cells

Wu,Su-Zhen; Lan,Yu-Yan; Chu,Chiao-Yun; Lee,Yi-Ping; Chang,Hong-Yi; Huang,Bu-Miin

doi:10.3892/mmr.2022.12913

Sodium arsenite and dimethylarsenic acid induces apoptosis in OC3 oral cavity cancer cells

Authors:
- Su-Zhen Wu
- Yu-Yan Lan
- Chiao-Yun Chu
- Yi-Ping Lee
- Hong-Yi Chang
- Bu-Miin Huang
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Affiliations: Department of Anesthesiology, Chi Mei Medical Center, Liouying, Tainan 73657, Taiwan, R.O.C., School of Medicine, College of Medicine, I‑Shou University, Kaohsiung 82445, Taiwan, R.O.C., Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan, R.O.C., Department of Biotechnology and Food Technology, College of Engineering, Southern Taiwan University of Science and Technology, Tainan 71005, Taiwan, R.O.C.
Published online on: December 13, 2022 https://doi.org/10.3892/mmr.2022.12913
Article Number: 26
Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Although arsenic is an environmental toxicant, arsenic trioxide (ATO) is used to treat acute promyelocytic leukemia (APL) with anticancer effects. Studies have demonstrated oral cancer is in the top 10 cancers in Taiwan. High rate of oral cancers is linked to various behaviors, such as excessive alcohol consumption and tobacco use. Similarly, betel chewing is a strong risk factor in oral cancer. In the present study, oral squamous carcinoma OC3 cells were investigated with the treatments of sodium arsenite (NaAsO2) and dimethylarsenic acid (DMA), respectively, to examine if arsenic compounds have anti‑cancer efforts. It was found that 1 µM NaAsO2 and 1 mM DMA for 24 h induced rounded contours with membrane blebbing phenomena in OC3 cells, revealing cell apoptotic characteristics. In addition, NaAsO2 (10‑100 µM) and DMA (1‑100 mM) significantly decreased OC3 cell survival. In cell cycle regulation detected by flow cytometry, NaAsO2 and DMA significantly augmented percentage of subG1 and G2/M phases in OC3 cells, respectively. Annexin V/PI double staining assay was further used to confirm NaAsO2 and DMA did induce OC3 cell apoptosis. In mechanism investigation, western blotting assay was applied and the results showed that NaAsO2 and DMA significantly induced phosphorylation of JNK, ERK1/2 and p38 and then the cleavages of caspase‑8, ‑9, ‑3 and poly ADP‑ribose polymerase (PARP) in OC3 cells, dynamically. In conclusion, NaAsO2 and DMA activated MAPK pathways and then apoptotic pathways to induce OC3 oral cancer cell apoptosis.

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