Rotundic acid enhances the impact of radiological toxicity on MCF-7 cells through the ATM/p53 pathway

Wang,Zhong-Feng; Sun,Wen-Yi; Yu,De-Hai; Zhao,Yan; Xu,Hong-Mei; He,Yu-Fang; Li,Hai-Jun

doi:10.3892/ijo.2018.4544

Rotundic acid enhances the impact of radiological toxicity on MCF-7 cells through the ATM/p53 pathway

Authors:
- Zhong-Feng Wang
- Wen-Yi Sun
- De-Hai Yu
- Yan Zhao
- Hong-Mei Xu
- Yu-Fang He
- Hai-Jun Li
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Affiliations: Department of Immunity, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Clinical Pharmacy and Pharmaceutical Management, School of Pharmaceutical Sciences in Jilin University, Changchun, Jilin 130021, P.R. China, Cancer Center, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, College of Chinese Medicinal Materials, Jilin Agriculture University, Changchun, Jilin 130000, P.R. China, Department of Obstetrics, The First Hospital, Jilin University, Changchun, Jilin 130021, P.R. China, Institute of Phytochemistry, Jilin Academy of Chinese Medicine Sciences, Changchun, Jilin 130000, P.R. China
Published online on: August 29, 2018 https://doi.org/10.3892/ijo.2018.4544
Pages: 2269-2277

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Abstract

Although radiation therapy is a powerful anticancer modality, radiation- induced stress response and gene expression with adaptive resistance may severely compromise the effectiveness of radiation. The function of rotundic acid (RA) on inducing apoptosis in the human breast cancer cell line MCF-7 has been investigated in a previous study. In the present study, the combined effect of chemotherapy and radiotherapy on reducing side effects was examined. The results of an MTT assay revealed that radiation (0.5, 2 and 10 Gy) effectively inhibit MCF-7 cell viability in a dose-dependent manner, consistent with the effects of RA (2, 5 and 12.5 µM). Interestingly, a lower dose of radiation (1 Gy) combined with RA (5 µM) exhibited a greater inhibition efficiency compared with a high dose of radiation alone. Flow cytometry revealed that radiation combined with RA induced the apoptosis of MCF-7 cells. Using western blotting, it was demonstrated that radiation induced the expression of ataxia-telangiectasia mutated (ATM) and p53 protein, and that RA enhanced this effect. On examining the potential underlying mechanism, it was revealed that radiation and RA combined induce Bcl-2-associated X protein expression and cell apoptosis in MCF-7 cells. An ATM inhibitor was able to restore the effect of radiation and RA on inducing MCF-7 cell apoptosis. These results suggest that the ATM/p53 pathway directly participates in radiation and RA-induced apoptosis in MCF-7 cells. RA has the potential for development as a novel drug for the treatment of human breast cancer combined with radiation therapy, given that the combined side effects are reduced.

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