Arsenic compounds induce apoptosis by activating the MAPK and caspase pathways in FaDu oral squamous carcinoma cells

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

doi:10.3892/ijo.2022.5308

Arsenic compounds induce apoptosis by activating the MAPK and caspase pathways in FaDu oral squamous carcinoma cells

Authors:
- Su-Zhen Wu
- Yu-Yan Lan
- Chiao-Yun Chu
- Yang-Kao Wang
- 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., Department of Nursing, Shu‑Zen Junior College of Medicine and Management, Kaohsiung 82144, 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: January 14, 2022 https://doi.org/10.3892/ijo.2022.5308
Article Number: 18

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Abstract

For a number of years, oral cancer has remained in the top ten most common types of cancer, with an incidence rate that is steadily increasing. In total, ~75% oral cancer cases are associated with lifestyle factors, including uncontrolled alcohol consumption, betel and tobacco chewing, and the excessive use of tobacco. Notably, betel chewing is highly associated with oral cancer in Southeast Asia. Arsenic is a key environmental toxicant; however, arsenic trioxide has been used as a medicine for the treatment of acute promyelocytic leukemia, highlighting its anticancer properties. The present study aimed to investigate the role of arsenic compounds in the treatment of cancer, using FaDu oral squamous carcinoma cells treated with sodium arsenite (NaAsO₂) and dimethyl arsenic acid (DMA). The results demonstrated that FaDu cells exhibited membrane blebbing phenomena and high levels of apoptosis following treatment with 10 µM NaAsO₂ and 1 mM DMA for 24 h. The results of cell viability assay demonstrated that the rate of FaDu cell survival was markedly reduced as the concentration of arsenic compounds increased from 10 to 100 µM NaAsO₂, and 1 to 100 mM DMA. Moreover, flow cytometry was carried out to further examine the effects of arsenic compounds on FaDu cell cycle regulation; the results revealed that treatment with NaAsO₂ and DMA led to a significant increase in the percentage of FaDu cells in the sub‑G1 and G2/M phases of the cell cycle. An Annexin V/PI double staining assay was subsequently performed to verify the levels of FaDu cell apoptosis following treatment with arsenic compounds. Furthermore, the results of the western blot analyses revealed that the expression levels of caspase‑8, ‑9 and ‑3, and poly ADP‑ribose polymerase, as well the levels of phosphorylated JNK and ERK1/2 were increased following treatment with NaAsO₂ and DMA in the FaDu cells. On the whole, the results of the present study revealed that treatment with NaAsO₂ and DMA promoted the apoptosis of FaDu oral cancer cells, by activating MAPK pathways, as well as the extrinsic and intrinsic apoptotic pathways.

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