Cryptotanshinone induces ROS-dependent autophagy in multidrug-resistant colon cancer cells

Publication date: 1 August 2017 Source:Chemico-Biological Interactions, Volume 273 Author(s): Zhenyu Xu, Hui Jiang, Yanhong Zhu, Huifang Wang, Jia Jiang, Lu Chen, Wenke Xu, Tao Hu, Chi Hin Cho The development of novel chemotherapeutic agents is highly desired for colon cancer treatment, in particular for the multidrug-resistant cancer types. Cryptotanshinone (CTS), an active quinoid diterpene isolated from Salvia miltiorrhiza Bunge, was previously reported to induce autophagy in various colon cancer cell lines. However, its mechanisms of action have not been fully understood. The current study aims to explore the mechanisms by which CTS induces autophagy in a multidrug-resistant human colon cancer cell line SW620 Ad300. Using MTT assay, CTS at 10 μM exhibited no significant cytotoxicity on human normal colon fibroblasts CCD-18Co, but induced 45.67% and 48.35% cell death in SW620 and SW620 Ad300 cells, respectively. Further studies revealed that CTS induced weak apoptosis (9.37%) and significant caspase-independent cell death in SW620 Ad300 cells. In the same cell line, CTS also induced significant autophagy, which was found to promote cell death and to mediate the cytotoxicity of CTS in these multidrug-resistant cells. Moreover, activation of ROS-p38 MAPK-NF-κB signaling pathway was involved in autophagic cell death induced by CTS in SW620 Ad300 cells. Interestingly, our results also demonstrated a complementary relationship between CTS-induced apoptosis and aut...
Source: Chemico Biological Interactions - Category: Biochemistry Source Type: research