Celastrol-induced apoptosis in human nasopharyngeal carcinoma is associated with the activation of the death receptor and the mitochondrial pathway

Lin,Heng‑Fu; Hsieh,Ming‑Ju; Hsi,Yi‑Ting; Lo,Yu‑Sheng; Chuang,Yi‑Ching; Chen,Mu‑Kuan; Chien,Su‑Yu

doi:10.3892/ol.2017.6346

Celastrol-induced apoptosis in human nasopharyngeal carcinoma is associated with the activation of the death receptor and the mitochondrial pathway

Authors:
- Heng‑Fu Lin
- Ming‑Ju Hsieh
- Yi‑Ting Hsi
- Yu‑Sheng Lo
- Yi‑Ching Chuang
- Mu‑Kuan Chen
- Su‑Yu Chien
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Affiliations: Department of Otorhinolaryngology, Head and Neck Surgery, Changhua Christian Hospital, Changhua 500, Taiwan, R.O.C., Cancer Research Center, Changhua Christian Hospital, Changhua 500, Taiwan, R.O.C., Department of Pharmacy, Changhua Christian Hospital, Changhua 500, Taiwan, R.O.C.
Published online on: June 8, 2017 https://doi.org/10.3892/ol.2017.6346
Pages: 1683-1690

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Abstract

Nasopharyngeal carcinoma (NPC) is a cancer that arises from the epithelium of the nasopharynx. Celastrol is a triterpene from traditional Chinese medicine, which demonstrates anti‑proliferative activity in several cancer cell lines. However, the effect of celastrol on human NPC and the underlying mechanisms are not yet elucidated. The present study investigated whether celastrol induced apoptosis in human NPC cells, and the underlying molecular mechanisms were explored. Celastrol decreased the viability of HONE‑1 and NPC‑039 cells in a dose‑dependent manner, and induced G1 and G2/M phase cell cycle arrest. The level of cleaved caspases‑3, ‑8, and ‑9 and poly (ADP‑ribose) polymerase 1 increased in cells treated with celastrol. There was an increase in active Bcl‑2‑like 11 isoform S, Bcl‑2‑associated X, Bcl‑2 antagonist/killer and truncated BH3‑interacting death antagonist, and the levels of the anti‑apoptotic Bcl‑2 and Bcl‑2‑like 1 decreased. Celastrol induced an increase in Fas, Fas‑associated via death domain, TNF receptor superfamily members (TNRSF) 1A and 10B, and TNFRSF1A associated via death domain, and induced a dose‑dependent reduction in mitochondrial membrane potential. Celastrol inhibited activation of mitogen‑activated protein kinase (MAPK) 1/3 and 14, and induced MAPK 8/9 activation. The results indicated that celastrol induced apoptosis through the death receptor and the mitochondrial pathway in human NPC cells, and is a promising candidate in the development of drugs against NPC.

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