Investigating the enhancement of cisplatin cytotoxicity on 5637 cells by combination with mogoltacin.
Transitional cell carcinomas (TCCs), which account for 90% of bladder cancers, arise from the transitional epithelium of bladder. Cisplatin is a chemotherapeutic drug used to treat bladder cancer, but intrinsic and acquired resistance to cisplatin limit its effectiveness. The aim of this study was to determine the ability of mogoltacin, a sesquiterpene-coumarin from Ferula badrakema, to enhance cytotoxic effects of cisplatin on 5637 cells, using MTT assay, comet method, DAPI staining and efflux assay. In order to analyse mogoltacin combinatorial effects, 5637 cells were cultured in the presence of various combined concentrations of mogoltacin and cisplatin. The results of MTT assay revealed that combination of 1 μg/mL cisplatin+32 μg/mL mogoltacin, increased the cytotoxicity of cisplatin by 45.3%. Investigating the mechanism of this action by comet assay indicated that mogoltacin increases the apoptotic effects of cisplatin on 5637 cells via DNA lesion by 44%. Furthermore, studying nuclear morphological changes revealed that the combination of mogoltacin+cisplatin significantly (P<0.001) increases the number of apoptotic cells. Results of efflux assay indicated that mogoltacin did not have any significant effect on the activity of MDR transporters, therefore, this sesquiterpene-coumarin increases the effects of cisplatin possibly by interacting with other drug transporters.
Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.
Fatemeh Behnam
FB
Rassouli
Maryam M
MM
Matin
Mehrdad
M
Iranshahi
Ahmad Reza
AR
Bahrami
Javad
J
Behravan
Samaneh
S
Mollazadeh
Vajiheh
V
Neshati
Fatemeh
F
Kalalinia
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D003374:Coumarins / Q000494:pharmacology*; D004249:DNA Damage; D018432:Drug Resistance, Multiple; D006801:Humans; D008942:Mitoxantrone / Q000493:pharmacokinetics; D012717:Sesquiterpenes / Q000494:pharmacology*
D000970:Antineoplastic Agents; D003374:Coumarins; D012717:Sesquiterpenes; C539928:mogoltacin; D008942:Mitoxantrone; D002945:Cisplatin