Cong Zu1, Guangyuan Qin1, Chunshu Yang1, Ning Liu1, Anning He1, Mingdi Zhang2, Xinyu Zheng3. 1. Lab 1, Cancer Institute of the First Affiliated Hospital, China Medical University, Shenyang, Liaoning, 110001, PR China. 2. Department of Breast Surgery, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, PR China. Electronic address: mingdizhangoct@163.com. 3. Lab 1, Cancer Institute of the First Affiliated Hospital, China Medical University, Shenyang, Liaoning, 110001, PR China; Department of Breast Surgery, First Affiliated Hospital, China Medical University, Shenyang, Liaoning, 110001, PR China. Electronic address: xyzheng@mail.cmu.edu.cn.
Abstract
PURPOSE: The resistance to 5-FU often limits its clinical effectiveness on breast cancer treatment. Combination therapy thus is employed to overcome this treatment resistance. We here report a potent antitumor effect of Emodin at low dose on chemotherapy sensitivity of MCF-7 breast cancer cells. METHODS: Cell viability, apoptosis, glutathiones (GSH) concentration and Reactive oxygen species (ROS) activity following Emodin and 5-FU treatment was assessed. Cellular senescence following combined treatment and silence of NRARP was examined by senescence-associated β-galactosidase analysis. Western blot analysis was used to determine changes in the expression of p21, p16, p27, E2F1 and NRARP. RESULTS: Low dose Emodin potentiates 5-FU-induced apoptosis of breast cancer cells, in association with inhibition of NRARP, resulting in cellular senescence. RNA interference of NRARP induced cellular senescence in MCF-7 breast cancer cells. Furthermore, the cellular senescence induced by Emodin and 5-FU treatment could be reverted by pcDNA-NRARP. CONCLUSION: These findings provide preclinical evidence for repurposing use of Emodin in combination with chemotherapeutic agents to treat breast cancer as an alternative salvage regimen.
PURPOSE: The resistance to 5-FU often limits its clinical effectiveness on breast cancer treatment. Combination therapy thus is employed to overcome this treatment resistance. We here report a potent antitumor effect of Emodin at low dose on chemotherapy sensitivity of MCF-7 breast cancer cells. METHODS: Cell viability, apoptosis, glutathiones (GSH) concentration and Reactive oxygen species (ROS) activity following Emodin and 5-FU treatment was assessed. Cellular senescence following combined treatment and silence of NRARP was examined by senescence-associated β-galactosidase analysis. Western blot analysis was used to determine changes in the expression of p21, p16, p27, E2F1 and NRARP. RESULTS: Low dose Emodin potentiates 5-FU-induced apoptosis of breast cancer cells, in association with inhibition of NRARP, resulting in cellular senescence. RNA interference of NRARP induced cellular senescence in MCF-7 breast cancer cells. Furthermore, the cellular senescence induced by Emodin and 5-FU treatment could be reverted by pcDNA-NRARP. CONCLUSION: These findings provide preclinical evidence for repurposing use of Emodin in combination with chemotherapeutic agents to treat breast cancer as an alternative salvage regimen.
Authors: Qing Zhang; Wen Wen Chen; Xue Sun; Die Qian; Dan Dan Tang; Li Lin Zhang; Mei Yan Li; Lin Yu Wang; Chun-Jie Wu; Wei Peng Journal: Int J Biol Sci Date: 2022-05-16 Impact factor: 10.750