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Despite widespread application of cisplatin in treatment of transitional cell carcinomas, its efficiency is far from satisfactory due to acquired drug resistance. The present study was carried out to estimate the effects of conferone, a sesquiterpene-coumarin isolated from Ferula badrakema, on increasing cisplatin cytotoxicity in 5637 cells. In order to determine conferone effects, 5637 cells were cultured in the presence of different concentrations of conferone and cisplatin in combination. The cytotoxicity and DNA damaging effects were then studied using MTT and comet assays, respectively. The results revealed that 24 h after the combination of 1 µg mL⁻¹ cisplatin with 32 µg mL⁻¹ conferone, the cytotoxicity of cisplatin was increased by 36.76%, and comet assay analyses showed that conferone could enhance the DNA damaging effects of cisplatin by 41%.

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., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Bladder cancer is one of the most common cancers worldwide, with the highest incidence in industrialized countries. There are three major histological subtypes of bladder cancer: transitional cell carcinoma (TCC) (> 90%), squamous cell carcinoma (< 10%) and adenocarcinoma (1-2%). The present study was carried out to assess the effects of conferone, a sesquiterpene coumarin isolated from Ferula badrakema, on a TCC subline, 5637 cells. In order to test the effects of conferone, 5637 cells were treated with different concentrations (16, 32, 64, 128 microg/ml) of conferone. The results indicated that conferone did not have any significant cytotoxic effect on these neoplastic cells. To determine the combining effects, the cells were cultured in the presence of different concentrations of conferone (16, 32, 64, 128 microg/ ml) and vincristine (30, 40, 50 microg/ml) in combination. The morphological changes were then observed and cytotoxicity effects were studied using the MTT assay 24, 48 and 72 h following drug administration. The cells were more rounded and granulated after treatments with both drugs in comparison to vincristine only. The results of the MTT assay confirmed the morphological observations. After 48 h of combined treatment with 40 microg/ml vincristine and 16 microg/ml conferone, the cytotoxicity of vincristine was increased by 23.6%.

Bladder cancer is the second common cancer of the genitourinary system throughout the world and intravesical chemotherapy is usually used to reduce tumour recurrence and progression. Human transitional cell carcinoma (TCC) is an epithelial-like adherent cell line originally established from primary bladder carcinoma. Here we report the effect of mogoltacin, a sesquiterpene coumarin from Ferula badrakema on TCC cells. Mogoltacin was isolated from the fruits of F. badrakema, using silica gel column chromatography and preparative thin layer chromatography. Mogoltacin did not have any significant cytotoxicity effect on neoplastic TCC cells at 16, 32, 64, 128, 200 and 600 microg ml(-1) concentrations. In order to analyse its combination effect, TCC cells were cultured in the presence of various combining concentrations of mogoltacin and vincristine. Cells were then observed for morphological changes (by light microscopy) and cytotoxicity using MTT assay. The effect of mogoltacin on vincristine toxicity was studied after 24, 48 and 72 h of drug administration. The results of MTT assay showed that mogoltacin can significantly enhance the cytotoxicity of vincristine and confirmed the morphological observations. Results revealed that combination of 40 microg ml(-1) vincristine with 16 microg ml(-1) mogoltacin increased the cytotoxicity of vincristine after 48 h by 32.8%.