Abstract: BACKGROUND:Imperatorin and osthol, the two coumarin derivatives from Apiacea family, have several anticancer activities. A large body of evidence demonstrates that these two coumarin derivatives regulates apoptosis, proliferation and invasion in different cancer types including ovarian, cervical, colon and prostate cancers as well as chronic myeloid leukemia etc., which are mediated by multiple signal transduction cascades. OBJECTIVE:In present study, the effects of imperatorin and osthol were compared with a known anticancer natural agent curcumin on 5-fluorourasil resistance in A549 cells. METHODS:Imperatorin (100–200 μM), osthol (100–200 μM), curcumin (100 μM) and/or 5-FU (64 μM) were applied on NSCLC cell line A549 and human bronchial epithelial cell line (Beas-2b) after a general concentration screening between 10 nM–1 mM and xCELLigence Real Time Cell Analysis (RTCA) was conducted to evaluate cytotoxic effects. RESULTS:100 μM curcumin indicated cytotoxic effect in A549 cells and when 5-FU alone did not show cytotoxic activity, it was observed that the cytotoxic effect of curcumin appeared to be similar when combined with 5-FU. 200 μM imperatorin/osthol, when used alone or in combination with 5-FU, showed a stronger cytotoxic effect on both cell lines. CONCLUSIONS:Imperatorin/osthol synergistically increased the efficacy of 5-FU in combination, but the same effect on healthy cells was observed as a limiting factor for future studies.
