Effect of CAPE (Caffeic Acid Phenethyl Ester) on drug resistance in leukemia cell lines

Objectives: Existence or development of drug resistance in patients with acute leukemia is one of major causes affecting the therapeutic failure. A resinous material collected by honey bees propolis, and its active component CAPE have antiinflammatory, antiviral and anticancer proporties. In this study, in leukemic cell lines including HL60, K562 and NB4 investigating the effects of CAPE to cell lines and drug resistance was aimed. Method: HL60, K562 and NB4 cell lines were incubated with azacytidine, decitabine, ara-C and CAPE at 37˚C for 4 days. Alteration of cell viability was evaluated using CellTiter-Glo® luminescent assay. Statistical analysis of obtained data was applied using the student t-test and p<0.05 was considered statistically significant. Findings: Viability assessment of K562, HL60 and NB4 cell lines after incubation with ara-C, azacytidine and decitabine revealed that all three cell lines were resistant against ara-C, whereas HL60 and NB4 cell lines were susceptible to azacytidine and decitabine while K562 cell line was resistant. To compare using ara-C alone and in combination with CAPE in HL60, K562 and NB4 cell lines, the viability diminished from 66.30% to 16.88% in K562 cell line and 83.24% to 10.05% in HL60 cell line respectively, and also the cell viability in NB4 cell line which has no reduction with ara-C decreased to 42.72% (p<0.001). Similarly, CAPE and decitabine concurrence in K562 cell line revealed the viability decrease from 60.65% to 23.99%, as compared to use decitabine alone (p<0.05). There has been no alteration in cell viability when used in combining of azacytidine with CAPE. Conclusion: As a result, in K562, HL60 and NB4 cell lines CAPE inhibits cell proliferation via its apoptotic, antioxidant effects, as well as by affecting MDR gene, kinase inhibition or membrane transport, reverses the drug-resistance, therefore can increase efficacy of chemotherapeutic agents and we believe the results obtained from our study should be supported by further research.