Andrographolide Synergized with Doxorubicin to Induce Cell Death in Breast Cancer Cell via ROS-dependent DNA Damage

Abstract

Abstract Breast cancer is a malignant tumor that seriously endangers women’s health all over the world. Doxorubicin is a commonly used chemotherapeutic drug for the treatment of breast cancer. However, its application is hindered by toxic side effects and drug resistance. A combination strategy must be found to increase the sensitivity of human breast cancer cells to doxorubicin and enhance its anticancer efficacy. Andrographolide (Andro) is a good candidate drug because of its good tolerance and anticancer efficacy. In this study, we found that andrographolide enhanced cell death caused by doxorubicin both in MDA-MB-231 and MCF-7 breast cancer cell lines. Furthermore, the combination treatment greatly increased the anti-cancer effect to MDA-MB-231 cell xenograft compared with every single treatment in Balb/c nude mouse model. Mechanistically, compared with andrographolide or doxorubicin alone treatment, the combined treatment significantly increased DNA damage by inducing ROS production, leading to cell death. In conclusion, andrographolide can be used to improve the sensitivity of doxorubicin in the treatment of breast cancer, providing a basis for the transformation of combined treatment into clinical application.