Osthole induces apoptosis of the HT‑29 cells via endoplasmic reticulum stress and autophagy

Zhou,Xing-Hua; Kang,Jian; Zhong,Zhen-Dong; Cheng,Yue

doi:10.3892/ol.2021.12987

Osthole induces apoptosis of the HT‑29 cells via endoplasmic reticulum stress and autophagy

Authors:
- Xing-Hua Zhou
- Jian Kang
- Zhen-Dong Zhong
- Yue Cheng
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Affiliations: Department of Anorectal Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610075, P.R. China, Animal Experiment Research Institute, Sichuan Provincial People's Hospital, Chengdu, Sichuan 610000, P.R. China
Published online on: August 10, 2021 https://doi.org/10.3892/ol.2021.12987
Article Number: 726
Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Endoplasmic reticulum stress (ERS) and autophagy are important pathways, which induce apoptosis of tumor cells. Osthole has been demonstrated to exert anticancer effects via the induction of apoptosis in several human colon cancer lines, but the mechanism underlying its involvement in the induction of ERS and autophagy in the human HT‑29 colorectal cancer cell line remains unknown. The present study aimed to identify the possible signaling pathways involved in osthole‑induced apoptosis of HT29 cells. Methodologically, colony formation and Cell Counting Kit‑8 assays were used to assess cell proliferation and viability, respectively, while flow cytometry was performed to investigate apoptosis. Signaling pathways, including apoptosis, autophagy and ERS, were also investigated in the HT‑29 cell line using western blot analysis. The results demonstrated that osthole inhibited cellular proliferation and viability in a dose‑dependent manner. In addition, osthole induced the expression level of proteins associated with mitochondria‑mediated cell apoptosis, autophagy and ERS. The association between autophagy and ERS in osthole‑induced apoptosis in the HT‑29 cell line was further clarified. Inhibiting cell autophagy with the inhibitor, 3‑methyladenine, suppressed osthole‑induced cell apoptosis and enhanced osthole‑induced ERS. By contrast, alleviating ERS with the inhibitor, 4‑phenylbutyric acid attenuated osthole‑induced cell apoptosis and autophagy. In conclusion, osthole could significantly suppress the proliferation and viability of the HT‑29 colorectal cancer cell line and induce cell apoptosis via autophagy and ERS. Furthermore, ERS may play a more important role in osthole‑induced cell apoptosis.

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