Suppression of NF-κB signaling and P-glycoprotein Function by Gambogic Acid Synergistically Potentiates Adriamycin -induced Apoptosis in Lung Cancer.

Suppression of NF-κB signaling and P-glycoprotein Function by Gambogic Acid Synergistically Potentiates Adriamycin -induced Apoptosis in Lung Cancer. Curr Cancer Drug Targets. 2013 Nov 12; Authors: Wang LH, Yang JY, Yang SN, Li Y, Ping GF, Hou Y, Cui W, Wang ZZ, Xiao W, Wu CF Abstract Gambogic acid (GA) has been approved by the Chinese Food and Drug Administration for the treatment of lung cancer in clinical trials. However, whether GA has chemosensitizing properties when combined with other chemotherapy agents in the treatment of lung cancer is not known. Here we investigated the effects of GA combined with adriamycin (ADM), a common chemotherapy agent, in regard to their activities and the possible mechanisms against lung cancer in vitro and in vivo. Cell viability results showed that sequential GA-ADM treatment was synergistic, while the reverse sequence and simultaneous treatments were antagonistic or additive, in lung cancer cells and ADM resistant cells, but not in normal cells. The combined use of GA and ADM synergistically displayed apoptosis-inducing activities in lung cancer cells. Moreover, GA in combination with ADM could promote PARP cleavage, enhance caspases activation and decrease the expression of anti-apoptotic proteins in lung cancer cells. The combined use of GA and ADM decreased the expression of P-glycoprotein and increased the accumulation of ADM in lung cancer cells. Furthermore, it was found that, prior to ADM treatme...
Source: Current Cancer Drug Targets - Category: Cancer & Oncology Authors: Tags: Curr Cancer Drug Targets Source Type: research