Enhancing Doxorubicin Efficacy in Non-Small Cell Lung Cancer: The Synergistic Role of Curcumin in Modulating p21 and p53

Lung cancer is one of the most lethal type of malignancy in the world. Polyphenolic compounds such as curcumin, which are found in certain plant foods, are considered as chemotherapeutic agents that induce their effect through their anti-proliferative, anti-estrogenic, and pro-oxidant properties associated with cancer. In this study, we investigated the effects of curcumin on the chemosensitivity of A549 cells to doxorubicin (DOX). A549 and A549/DOX cancer cells treated with DOX and curcumin and MTT assay was applied to investigate the cell viability. Western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were applied to investigate the protein and mRNA expression levels of P-glycoprotein (p-gp), apoptosis mediators, p21 and p53. P-gp activity was assessed by rhodamine 123 accumulation assay. Apoptosis was measured by annexin V flow cytometry. Curcumin potentiated the anticancer effects of DOX in A549/DOX cells. In other words, combinational treatment of resistant cells with DOX and curcumin reversed resistant phenotype in NSCLC via downregulating P-gp and p21 and upregulating p53. In addition, cells exposed to curcumin showed higher levels of apoptosis and higher expression levels of pro-apoptotic mediators. In conclusion, our findings demonstrated the possible effective roles of curcumin in the reversing DOX resistance via targeting p21 and p53 in NSCLC.