Natural borneol is a novel chemosensitizer that enhances temozolomide-induced anticancer efficiency against human glioma by triggering mitochondrial dysfunction and reactive oxide species-mediated oxidative damage.
Wen-Jian Liu, Yi-Bo Yin, Jing-Yi Sun, Sai Feng, Jin-Kui Ma, Xiao-Yan Fu, Ya-Jun Hou, Ming-Feng Yang, Bao-Liang Sun, Cun-Dong Fan
Author Information
Wen-Jian Liu: Department of Neurology, Affiliated Hospital of Taishan Medical University, Taian, Shandong, People's Republic of China, tblsun66@163.com.
Yi-Bo Yin: Department of Neurology, Affiliated Hospital of Taishan Medical University, Taian, Shandong, People's Republic of China, tblsun66@163.com.
Jing-Yi Sun: Department of Orthopaedics, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Gangwon, Korea.
Sai Feng: Guangzhou New BenFu Technology Co., Ltd, Guangzhou, Guangdong, People's Republic of China.
Xiao-Yan Fu: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong, People's Republic of China, tblsun66@163.com, tcdfan66@163.com.
Ya-Jun Hou: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong, People's Republic of China, tblsun66@163.com, tcdfan66@163.com.
Ming-Feng Yang: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong, People's Republic of China, tblsun66@163.com, tcdfan66@163.com.
Bao-Liang Sun: Department of Neurology, Affiliated Hospital of Taishan Medical University, Taian, Shandong, People's Republic of China, tblsun66@163.com.
Cun-Dong Fan: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong, People's Republic of China, tblsun66@163.com, tcdfan66@163.com.
BACKGROUND: Temozolomide (TMZ)-based chemotherapy represents an effective way for treating human glioma. However, its clinical application is limited because of its side effects and resistance to standard chemotherapy. Hence, the search for novel chemosensitizers to augment their anticancer efficiency has attracted much attention. Natural borneol (NB) has been identified as a potential chemosensitizer in treating human cancers. However, the synergistic effect and mechanism of NB and TMZ in human glioma have not been investigated yet. MATERIALS AND METHODS: U251 human glioma cells were cultured, and the cytotoxicity and apoptosis of NB and/or TMZ were examined by MTT assay, flow cytometric analysis and Western blot. Nude mice tumor model was also employed to evaluate the in vivo anticancer effect and mechanism. RESULTS: The results showed that the combined treatment of NB and TMZ more effectively inhibited human glioma growth via triggering mitochondria-mediated apoptosis in vitro, accompanied by the caspase activation. Combined treatment of NB and TMZ also caused mitochondrial dysfunction through disturbing Bcl-2 family expression. Further investigation revealed that NB enhanced TMZ-induced DNA damage through inducing reactive oxide species (ROS) overproduction. Moreover, glioma tumor xenograft growth in vivo was more effectively inhibited by the combined treatment with NB and TMZ through triggering apoptosis and anti-angiogenesis. CONCLUSION: Taken together, our findings validated that the strategy of using NB and TMZ could be a highly efficient way to achieve anticancer synergism.
