Mechanism of HN‑3 cell apoptosis induced by carboplatin: Combination of mitochondrial pathway associated with Ca2+ and the nucleus pathways

Shen,Bo; Mao,Wenjing; Ahn,Jin‑Chul; Chung,Phil‑Sang; He,Peijie

doi:10.3892/mmr.2018.9507

Mechanism of HN‑3 cell apoptosis induced by carboplatin: Combination of mitochondrial pathway associated with Ca2+ and the nucleus pathways

Authors:
- Bo Shen
- Wenjing Mao
- Jin‑Chul Ahn
- Phil‑Sang Chung
- Peijie He
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Affiliations: Institute of Radiation Medicine, Fudan University, Shanghai 200032, P.R. China, Department of Otolaryngology‑Head and Neck Surgery, Shanghai Key Clinical Disciplines of Otorhinolaryngology, Eye and ENT Hospital of Fudan University, Shanghai 200031, P.R. China, Department of Otolaryngology‑Head and Neck Surgery, Dankook University, Cheonan, Chungcheongnam 330‑715, Republic of Korea
Published online on: September 24, 2018 https://doi.org/10.3892/mmr.2018.9507
Pages: 4978-4986
Copyright: © Shen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Laryngeal carcinomas have been recognized as a serious health threat worldwide. In the present study, the mechanism of apoptosis in HN‑3 cells induced by carboplatin (CBCDA), a widely used anti‑cancer drug, was investigated. The pro‑apoptotic effect of CBCDA in HN‑3 cells was demonstrated to be time‑ and dose‑dependent. Therefore, the stages of apoptosis were investigated in chronological order. The results demonstrated that excessive generation of cytosolic Ca2+ in HN‑3 cells was initially triggered when cells were exposed to CBCDA, followed by the appearance of mitochondrial depolarization and oxidative stress, leading to the release of apoptosis‑inducing factor. At later stages, expression of caspase‑8 was increased due to the apoptotic signals originating from CBCDA‑induced DNA damage, as well as caspase‑9 and poly ADP ribose polymerase (PARP) expression upregulation. Glutathione decreased the available CBDCA concentration, decreased apoptosis and alleviating oxidative stress, thus reducing the actual effective concentration. Mechanistic research may benefit the rational design of more efficient therapeutic strategies as well as development of novel platinum‑based agents.

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