Enhanced anticancer efficiency of doxorubicin against human glioma by natural borneol through triggering ROS-mediated signal

• Main Authors: Wen-qiang Cao, Ying Li, Ya-jun Hou, Mao-xun Yang, Xue-qi Fu, Bai-song Zhao, Han-ming Jiang, Xiao-yan Fu
• Format: Article
• Language: English
• Published: Elsevier 2019-10-01
• Series: Biomedicine & Pharmacotherapy
• Subjects: Doxorubicin; Natural borneol; ROS; DNA damage; Chemosensitizer
• Online Access: http://www.sciencedirect.com/science/article/pii/S0753332219319304

Doxorubicin (DOX) as a first-line chemotherapeutic drug has been widely used for therapy of human cancers. However, side effects and chemo-resistance severely blocked its clinic application. Herein, natural borneol (NB) as a novel monoterpenoid chemosensitizer was found to have the potential to increase the blood brain barrier (BBB) permeability and intracellular uptake of DOX in vitro, and synergistically enhanced DOX-induced cytotoxicity in human glioma cells. NB treatment significantly potentiated DOX-induced G2/M cell cycle arrest by triggering reactive oxygen species (ROS)-mediated DNA damage. NB also enhanced DOX-induced dysfunction of MAPKs and PI3 K/AKT pathways. Furthermore, U251 human glioma xenograft growth in vivo was also effectively inhibited by combined treatment of DOX with NB through induction of G2/M-phase arrest and antiangiogenesis. Taken together, our finding validated that NB could act as novel chemosensitizer to enhance DOX-induced anticancer efficacy, and strategy of using NB and DOX could be a high efficient way in therapy of human cancers.