Abstract
Acquired resistance to chemotherapy of anticancer drug paclitaxel is the problem during cancer treatment. To investigate the drug resistance, we established a paclitaxel-resistant mutant cell line called H460/TAX cells derived from human non-small cell lung cancer parental H460 cells. Nuclear factor kB (NF-kB) activation is associated with inducible chemoresistance. Many anti-cancer drugs are able to activate NF-kB. Paclitaxel is also one of anti-neoplastic drugs that activate NF-kB. Inhibition of NF-kB could sensitize cell to chemotherapy-induced apoptosis. Here, we examined the effect of caffeic acid phenethyl ester (CAPE) on paclitaxel resistance. CAPE, an active ingredient of propolis from honeybee hives, is known to have anti-inflammatory, anti-virus and anti-cancer properties. CAPE is a modulator capable of preventing the translocation of the p65 subunit of NF-kB to the nucleus. Recently, we found that pretreated cancer cells with CAPE (5 mM, 7 days) could decrease the drug resistance of mutant H460/TAX cells from 6.27 fold to 1.83 fold. Partial toxicity is found as the higher dose of CAPE; therefore, the low dose and long term CAPE pretreatment recover the drug sensitivity of mutant H460/TAX cells without poisoning the parental H460 cells. Mutant H460/TAX cells show higher p65 (subunit of NF-kB) and lower level of IKBa than parental H460 cells. Decreasing of resistance in mutant H460/TAX cells by the pretreatment of CAPE also reduces the paclitaxel induced NF-kB activation. Taken together, our results support the involvement of NF-kB in paclitaxel induced resistance, and CAPE is a potent modulator of NF-kB activity to improve the clinical efficacy of paclitaxel in lung cancer treatment.