Cb-Pic Sensitizes Chemoresistant Cancer Cells To Drugs Via Suppression Of Mdr1 And Its Upstream Signal Molecules, Akt And P38-Mapk

ATP-binding cassette (ABC) transporters including MDR1-/P-gp have been majorly targeted for drug resistant tumor therapies. In this study, we screened the compound that negatively affects MDR-1 expression in chomoresistant cancer cell lines. We found that CB-PIC, the novel synthetic compound, could decrease P-glycoprotein expression via disrupt AKT/p-38 signal pathway in paclitaxel resistant lung cancer cell, H460/PR and doxorubicin resistant breast cancer cell, MCF7/Adr with highly expressed P-glycoprotein. However, CB-PIC did not regulate enzyme activity of P-glycoprotein, while EGCG and tannic acid accumulated Rhodamine 123 intracellular region of cell via short time efflux assay. CB-PIC treatment resulted in disruption of proliferation of drug resistant cells. In addition, CB-PIC dramatically induced apoptosis in time and dose dependent manner in both paclitaxel and doxorubicin resistant cancer cells. Furthermore, CB-PIC sensitizes drug-resistant cancer cells to paclitaxel and doxorubicin by decrease of survival proteins, survivin, Mcl-1 and Bcl-2, as well as MDR1 suppression leading to accumulate the treated drug intracellular region. Taken together, CB-PIC suppresses the P-glycoprotein expression through inhibition of AKT/p-38 MAPK signaling resulting in the increase of drug sensitivity in chemoresistant cancer cells. Citation Format: Duckgue Lee, Miyong Yun. CB-PIC sensitizes chemoresistant cancer cells to drugs via suppression of MDR1 and its upstream signal molecules, AKT and p38-MAPK. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 768. doi:10.1158/1538-7445.AM2014-768