Norcantharidin inhibits the malignant progression of cervical cancer by inducing endoplasmic reticulum stress

Zhang,Zhongbao; Sun,Beibei; Lu,Jinqiu; Bai,Penglai; Su,Yu; Li,Yanchun

doi:10.3892/mmr.2024.13195

Norcantharidin inhibits the malignant progression of cervical cancer by inducing endoplasmic reticulum stress

Authors:
- Zhongbao Zhang
- Beibei Sun
- Jinqiu Lu
- Penglai Bai
- Yu Su
- Yanchun Li
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Affiliations: Department of Gynecology, Tongliao City Hospital, Tongliao, Inner Mongolia Autonomous Region, P.R. China
Published online on: March 7, 2024 https://doi.org/10.3892/mmr.2024.13195
Article Number: 71
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The antitumor effect of norcantharidin (NCTD) has been widely reported. However, whether NCTD can inhibit cervical cancer remains unknown. In the present study, it was shown that NCTD inhibited the viability of cervical cancer cells and caused cell cycle arrest in a concentration‑dependent manner. Further analysis revealed that the NCTD‑induced reduction in cell viability could be reversed by the inhibitor of apoptosis z‑VAD‑FMK and by the inhibitor of endoplasmic reticulum (ER) stress, 4‑phenylbutyric acid (4‑PBA). Additionally, NCTD led to the accumulation of reactive oxygen species as well as a decrease in the mitochondrial membrane potential in cervical cancer cells, whereas 4‑PBA pre‑treatment attenuated these alterations. In addition, NCTD increased the expression of the apoptosis‑related proteins Bip, activating transcription factor (ATF) 4 and C/EBP homologous protein in a concentration‑dependent manner. Moreover, NCTD significantly increased the expression of the ER stress‑related signaling molecules protein kinase R‑like ER kinase, inositol‑requiring enzyme 1 and ATF6, but 4‑PBA abolished these effects. In vivo experiments showed that NCTD significantly inhibited the growth of subcutaneous tumors in mice. Additionally, the expression of ER stress‑related molecules and apoptosis‑related proteins increased significantly after NCTD treatment. In conclusion, NCTD induces apoptosis by activating ER stress and ultimately curtails the progression of cervical cancer.

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