Reversal of P ‑Glycoprotein-Mediated Multidrug Resistance by Novel Curcumin Analogues in Paclitaxel-resistant Human Breast Cancer Cells.

Reversal of P‑Glycoprotein-Mediated Multidrug Resistance by Novel Curcumin Analogues in Paclitaxel-resistant Human Breast Cancer Cells. Biochem Cell Biol. 2020 Jan 22;: Authors: Gao L, Zhao P, Li Y, Yang D, Hu P, Li L, Cheng Y, Yao H Abstract Multidrug resistance (MDR) is a major obstacle for successful cancer chemotherapy and the main cause of MDR has been attributed to P-glycoprotein (P-gp) overexpression. In the present study, four P-gp modulators (E,E)-4,6-bis(styryl)-2-(substituted amino)-pyrimidines were evaluated for their activity in a P-gp overexpressed breast cancer cell line LCC6MDR. The four modulators displayed significantly better P-gp modulating activity compared to the positive control verapamil (RF=5.4), with a relative fold (RF) increase in activity ranging from 33.3 to 86.0, In contrast to compounds <b>a</b> and <b>c</b> that exhibited lower cytotoxicity, compounds <b>b</b> and <b>d</b> were non-toxic towards both cancer cells and normal cells, with IC<sub>50</sub> values greater than 100 μM. RT-qPCR results demonstrated that after exposure to 2 μM compounds <b>a</b>, <b>b</b>, <b>c</b> and <b>d</b>, the MDR1 mRNA expression level in LCC6MDR cells decreased to 45, 50, 38, and 51%, respectively. However,western-blot results indicated that compound <b>c</b> was able to reverse P-gp mediated MDR,...
Source: Biochemistry and Cell Biology - Category: Biochemistry Authors: Tags: Biochem Cell Biol Source Type: research