Salvianolic acid B renders glioma cells more sensitive to radiation via Fis-1-mediated mitochondrial dysfunction

• Published in: Biomedicine & pharmacotherapy 2018-11, Vol.107, p.1230-1236
• Main Authors: Chen, Wei, Wang, Ning, Li, Rui-Chun, Xu, Gao-Feng, Bao, Gang, Jiang, Hai-Tao, Wang, Mao-De
• Format: Article
• Language: English
• Subjects: Apoptosis - drug effects; Apoptosis - radiation effects; Benzofurans - pharmacology; Brain Neoplasms - pathology; Cell Line, Tumor; Cell Survival - drug effects; Cell Survival - radiation effects; Drugs, Chinese Herbal - pharmacology; Gene Knockdown Techniques; Glioma; Glioma - pathology; Humans; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondria - radiation effects; Mitochondrial fission; Mitochondrial Proteins - genetics; Mitochondrial Proteins - metabolism; Neurons - drug effects; Neurons - pathology; Neurons - radiation effects; Radiation sensitivity; Radiation, Ionizing; Radiation-Sensitizing Agents - pharmacology; RNA, Small Interfering - genetics; Salvianolic acid B
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2018.08.113

Glioma remains the leading cause of brain tumor-related death worldwide, and radiation is a standard adjuvant therapy with proven efficacy. Salvianolic acid B (SalB), a bioactive compound isolated from Radix Salviae, has been shown to exert anti-cancer effects in many cancer cell lines, including glioma. This study aimed to investigate whether SalB could affect response to radiation in human glioma cells. We found that SalB decreased cell viability of U87 cells in a-dose-dependent manner. A subthreshold dose of SalB at 0.5 μM, which had no effect on cell viability and apoptosis, significantly increased radiation sensitivity of U87 cells in a dose- and time-dependent manner, but had no effect on sensitivity to temozolomide (TMZ). Similar results were also observed in human glioma U373 cells. In addition, SalB aggravated the radiation-induced apoptosis and mitochondrial dysfunction, as measured by mitochondrial Ca2+ buffering capacity and mitochondrial swelling. SalB treatment markedly promoted mitochondrial fission and differently regulated the expression of fission proteins. Furthermore, downregulation of the fission protein Fis-1 using siRNA was found to partially reversed the SalB-induced effects on cell viability, apoptosis and mitochondrial fission in U87 cells. In conclusion, our results suggest that a subthreshold dose of SalB renders glioma cells more sensitive to radiation via Fis-1-mediated mitochondrial dysfunction, and radiotherapy combined with SalB might be a novel treatment for glioma patients.