Chien-Hsing Lee1, Chiung-Wei Huang2, Po-Chih Chang3, Jun-Ping Shiau4, In-Pin Lin5, Mei-Ying Lin6, Chih-Cheng Lai7, Chung-Yi Chen8. 1. Department of Pharmacology, Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, and Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan. Electronic address: chlee0818@kmu.edu.tw. 2. Department of Physiology, Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. 3. Division of Thoracic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan; Weight Management Center, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan; College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. 4. Division of Breast Surgery, Department of Surgery, Kaohsiung Medical University Hospital, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. 5. Department of Pharmacology, Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, and Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan. 6. Community Health Promotion Center, Kaohsiung Municipal CiJin Hospital, Kaohsiung 80708, Taiwan. 7. Department of Intensive Care Medicine, Chi Mei Medical Center, Liouying, Tainan 73659, Taiwan. Electronic address: dtmed141@gmail.com. 8. Department of Nutrition and Health Science, School of Medical and Health Sciences, Fooyin University, Kaohsiung 83102, Taiwan. Electronic address: xx377@fy.edu.tw.
Abstract
BACKGROUND: Syringin (Syr), a phenylpropanoid glycoside extracted from Eleutherococcus senticosus, possesses various biological properties, including anticancer activities. However, the cytotoxicity effects of Syr on breast cancer have not yet been elucidated. PURPOSE: In this study, we evaluated the anticancer potential of Syr on breast carcinoma and the mechanism involved. STUDY DESIGN/ METHODS: Non-tumorigenic (M10), tumorigenic (MCF7) and metastatic (MDA-MB-231) breast cancer cell lines as well as xenograft model were treated with Syr. Proliferation and cell cycle distribution were evaluated using the MTT, the colony formation assay and flow cytometry. The expression levels of cytotoxicity-related proteins were detected by Western blot. RESULTS: Here, we found that colony formation inhibition, cell cycle arrest in the G2/M phase, down-regulation of X-linked inhibitor of apoptosis protein (XIAP), cleaved poly (ADP-ribose) polymerase (PARP) and caspase-3/9 activation were observed in MCF7 and MDA-MB-231 cells treated with Syr. Moreover, pretreatment with a pan-caspase inhibitor (Z-DEVD-FMK) inhibited Syr-induced apoptosis. In addition, treatment with Syr also increased the production of reactive oxygen species (ROS). However, the antioxidant N-acetyl-cysteine (NAC) reversed the ROS levels and rescued the apoptotic changes. Meanwhile, Syr inhibited the growth of breast cancer xenograft models and dramatically decreased tumor volume without any obvious body weight loss in vivo. CONCLUSION: Our findings suggest that Syr induces oxidative stress to suppress the proliferation of breast cancer and thus might be an effective therapeutic agent to treat breast cancer.
BACKGROUND: Syringin (Syr), a phenylpropanoid glycoside extracted from Eleutherococcus senticosus, possesses various biological properties, including anticancer activities. However, the cytotoxicity effects of Syr on breast cancer have not yet been elucidated. PURPOSE: In this study, we evaluated the anticancer potential of Syr on breast carcinoma and the mechanism involved. STUDY DESIGN/ METHODS: Non-tumorigenic (M10), tumorigenic (MCF7) and metastatic (MDA-MB-231) breast cancer cell lines as well as xenograft model were treated with Syr. Proliferation and cell cycle distribution were evaluated using the MTT, the colony formation assay and flow cytometry. The expression levels of cytotoxicity-related proteins were detected by Western blot. RESULTS: Here, we found that colony formation inhibition, cell cycle arrest in the G2/M phase, down-regulation of X-linked inhibitor of apoptosis protein (XIAP), cleaved poly (ADP-ribose) polymerase (PARP) and caspase-3/9 activation were observed in MCF7 and MDA-MB-231 cells treated with Syr. Moreover, pretreatment with a pan-caspase inhibitor (Z-DEVD-FMK) inhibited Syr-induced apoptosis. In addition, treatment with Syr also increased the production of reactive oxygen species (ROS). However, the antioxidant N-acetyl-cysteine (NAC) reversed the ROS levels and rescued the apoptotic changes. Meanwhile, Syr inhibited the growth of breast cancer xenograft models and dramatically decreased tumor volume without any obvious body weight loss in vivo. CONCLUSION: Our findings suggest that Syr induces oxidative stress to suppress the proliferation of breast cancer and thus might be an effective therapeutic agent to treat breast cancer.
Authors: Getinet M Adinew; Equar Taka; Bereket Mochona; Ramesh B Badisa; Elizabeth A Mazzio; Rashid Elhag; Karam F A Soliman Journal: Nutrients Date: 2021-12-25 Impact factor: 5.717