Synergistic effect of coumarine derivatives imperatorin and osthol on 5-fluorourasil cytotoxicity on nonsmall cell lung cancer cells

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Uzunhisarcıklı E. , Karaboğa Arslan A. K. , Aycan M. B.

Journal of Cellular Biotechnology, vol.5, no.1, pp.71-77, 2019 (Refereed Journals of Other Institutions) identifier

  • Publication Type: Article / Article
  • Volume: 5 Issue: 1
  • Publication Date: 2019
  • Doi Number: 10.3233/jcb-189015
  • Title of Journal : Journal of Cellular Biotechnology
  • Page Numbers: pp.71-77


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 M), osthol (100–200 M), curcumin (100 M) and/or 5-FU (64 M) 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 M 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 M 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.