Investigating Cytotoxic and Anticancer Properties of Coumarin Derivatives Contain Geranyl Groups at Different Position on Cervical Cancer

Background and Aim: Coumarin compounds have been known topossess anti-inflammatory, antioxidant, antiallergic, hepatoprotective,antithrombotic, antimicrobial, anti-arrhythmic, anti-osteoporosis,antiviral, and anticarcinogenic activities. Due to this wide variety ofpharmacological values, coumarins and its derivatives have receivedmore attention in synthesis and production.Methods: In the present study, we aimed to investigate the effect of geranylposition on coumarin backbone on the cytotoxicity of these syntheticcompounds. To do so, first, the cytotoxic effect of 3-geranyloxycoumarin(3-GC), 4-geranyloxycoumarin (4-GC), 5-geranyloxycoumarin (5-GC),6-geranyloxycoumarin (6-GC), 7-geranyloxycoumarin (7-GC) and8-geranyloxycoumarin (8-GC) were assessed by MTT assay on HeLa(cervical cancer) and HDF (human dermal fibroblast) cells. Furthermore,the apoptosis-inducing potential of these coumarin compounds wasdetermined by flow cytometry.Results: The results of the MTT assay revealed that 3-GC, 4-GC, 5-GC,6-GC, and 8-GC had significant cytotoxic effects on HeLa cells. Whilethey did not show any significant cytotoxicity on normal HDF cells.Moreover, the flow cytometric analysis, using PI/ FITC-Annexin V, showedthat 3-GC, 4-GC, 5-GC, 6-GC and 8-GC induced apoptosis in HeLacancer cells. Thus, they can be used as potent anticancer compounds.Conclusion: Altogether, our results indicate that changes in the levelof cellular toxicity on HeLa cells are associated with the position ofthe geranyl group; which puts an emphasis on the importance of therelationship between structure and activity in coumarin compounds. Ourresults showed that position 6 was the best site for the geranyl group.Further studies on various cancer cell lines are required to confirmthese findings and future studies need to be focused on the molecularmechanisms of toxicity inducing potential of these compounds both invitro and in vivo.

کلیدواژه ها:

Cervical cancer ، Anticancer ، Geranyloxycoumarin