Arsenic compounds activate the MAPK and caspase pathways to induce apoptosis in OEC-M1 gingival epidermal carcinoma

Ning Ping Foo, Chi Lin Ko, Chiao Yun Chu, Chia-Yih Wang, Edmund Cheung So, Bu Miin Huang

Research output: Contribution to journalArticlepeer-review

Abstract

Arsenic is a well-documented environmental toxicant that can induce neurotoxicity and peripheral vascular diseases. In fact, arsenic trioxide has been used to treat various cancer types. Oral cancer has been in the top ten common cancers for decades in Taiwan, and the incidence rate is continuously increasing. The majority of oral cancers are associated with excessive tobacco, alcohol consumption and betel chewing. To the best of our knowledge, no study has revealed the effect of arsenic compounds on oral cancers. Thus, the present study used OEC-M1 oral squamous carcinoma cells treated with sodium arsenite (NaAsO2) and dimethylarsenic acid (DMA) to determine whether both arsenic compounds could exert anticancer effects on oral cancer. The results demonstrated that NaAsO2and DMA induced rounding up and membrane blebbing in OEC-M1 cells, which are morphological characteristics of apoptosis. Annexin V/PI double staining analysis further confirmed that both arsenic compounds induced apoptosis of OEC-M1 cells. In addition, NaAsO2and DMA significantly decreased the survival rate and increased the percentage of OEC-M1 cells in the subG1 and G2/M phases (P<0.05). Furthermore, both arsenic compounds significantly activated the cleavage of caspase-8, -9, -3 and PARP, and the phosphorylation of JNK, ERK1/2 and p38 in OEC-M1 cells (P<0.05). Collectively, the findings of the present study indicated that NaAsO2and DMA stimulate extrinsic and intrinsic apoptotic pathways through the activation of the MAPK pathways to induce apoptosis of OEC-M1 cells, suggesting that NaAsO2and DMA may be used as novel anticancer drugs for oral cancers.

Original languageEnglish
Pages (from-to)2701-2714
Number of pages14
JournalOncology Reports
Volume44
Issue number6
DOIs
Publication statusPublished - 2020 Dec

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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