Myricetin induces apoptosis via endoplasmic reticulum stress and DNA double-strand breaks in human ovarian cancer cells

Xu,Ye; Xie,Qi; Wu,Shaohua; Yi,Dan; Yu,Yang; Liu,Shibing; Li,Songyan; Li,Zhixin

doi:10.3892/mmr.2016.4763

Myricetin induces apoptosis via endoplasmic reticulum stress and DNA double-strand breaks in human ovarian cancer cells

Authors:
- Ye Xu
- Qi Xie
- Shaohua Wu
- Dan Yi
- Yang Yu
- Shibing Liu
- Songyan Li
- Zhixin Li
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Affiliations: Medical Research Laboratory, Jilin Medical University, Changchun, Jilin 132013, P.R. China, Department of Pathophysiology, Basic Medical College, Jilin University, Changchun, Jilin 130021, P.R. China, Department of Medical Laboratory, Jilin Medical University, Changchun, Jilin 132013, P.R. China, Medical Examination Center, Jilin Traditional Chinese and Western Medicine Hospital, Changchun, Jilin 132010, P.R. China, Department of Histology and Embryology, Jilin Medical University, Changchun, Jilin 132013, P.R. China
Published online on: January 12, 2016 https://doi.org/10.3892/mmr.2016.4763
Pages: 2094-2100
Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The mechanisms underlying myricetin-induced cancer cell apoptosis remain to be elucidated. Certain previous studies have shown that myricetin induces apoptosis through the mitochondrial pathway. Apoptosis, however, can also be induced by other classical pathways, including endoplasmic reticulum (ER) stress and DNA double‑strand breaks (DSBs). The aim of the present study was to assess whether these two apoptotic pathways are involved in myricetin‑induced cell death in SKOV3 ovarian cancer cells. The results revealed that treatment with myricetin inhibited viability of SKOV3 cells in a dose‑dependent manner. Myricetin induced nuclear chromatin condensation and fragmentation, and also upregulated the protein levels of active caspase 3 in a time‑dependent manner. In addition, myricetin upregulated ER stress‑associated proteins, glucose‑regulated protein‑78 and C/EBP homologous protein in SKOV3 cells. Phosphorylation of H2AX, a marker of DNA DSBs, was revealed to be upregulated in myricetin-treated cells. The data indicated that myricetin induces DNA DSBs and ER stress, which leads to apoptosis in SKOV3 cells.

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