Quinacrine and Curcumin synergistically increased the breast cancer stem cells death by inhibiting ABCG2 and modulating DNA damage repair pathway.

Quinacrine and Curcumin synergistically increased the breast cancer stem cells death by inhibiting ABCG2 and modulating DNA damage repair pathway. Int J Biochem Cell Biol. 2019 Dec 23;:105682 Authors: Nayak D, Tripathi N, Kathuria D, Siddharth S, Nayak A, Bharatam PV, Nath Kundu C Abstract Cancer stem cell like cells (CSCs) present a challenge in the management of cancers due to their involvement in the development of resistance against various chemotherapeutic agents. Over expression of ABCG2 transporter gene is one of the factors responsible for drug resistance in CSCs, which causes efflux of therapeutic drugs from these cells. The development of inhibitors against CSCs has not achieved any significant success, till date. In this work, we have evaluated the anti-proliferative activity of curcumin (Cur) and quinacrine (QC) against CSCs using in vitro model system. Cur and QC synergistically inhibited the proliferation, migration and invasion of CSCs enriched side population (SP) cells of cigarette smoke condensate induced breast epithelial transformed (MCF-10A-Tr) generated metastatic cells. Cur + QC combination increased the DNA damage and inhibited the DNA repair pathways in SP cells. Uptake of QC increased in Cur pre-treated SP cells and this combination inhibited the ABCG2 activity by the reduction of ATP hydrolysis in cells. In vitro DNA binding reconstitution system suggests that QC specifically binds to DNA and caused DNA...
Source: The International Journal of Biochemistry and Cell Biology - Category: Biochemistry Authors: Tags: Int J Biochem Cell Biol Source Type: research