Cytarabine(cyt) is the drug of choice in treatment of acute myeloid leukemia(AML). Various tumor markers like cytokines (TNF-α, interleukins like IL-6, IL-8, IL-10), transcription factors like NF-κB and their downstream signalling pathways are aberrantly expressed in this form of leukemia. Cytarabine acts by modulating these proteins. However, cytarabine poses several harmful effects and development of drug resistance is a common phenomenon, which negatively affects therapeutic outcome. During drug resistance, the above-mentioned proteins are further deregulated. Cytarabine resistance is characterized by high expression of multi-drug resistant proteins p-glycoprotein and MRP. To overcome the adverse effects of cytarabine, non-toxic means is preferred for a better result. This study aimed to tackle these problems using phytochemical curcumin. HL-60 cells were exposed to increasing doses of cyt and a drug resistant cell HL-60R was developed, which was found to be resistant to other drugs used in AML therapy. Cyt regulates the aberrant expressions of markers and induces apoptosis in HL-60 cells; the modulation gets enhanced in presence of curcumin. In HL-60R, cyt hardly showed any effect; however, when curcumin was administered to cells in combination with cyt, the tumor markers were found to be modulated by cyt, thus rendering the resistant cells sensitive to the drug. The results obtained highlight the potential of curcumin in enhancing the efficacy of cyt and overcoming drug resistance in AML. Thus, this study shows that curcumin may effectively be used as an adjuvant therapy in AML, though intense clinical studies are warranted in this regard.
