The enhancement of vincristine cytotoxicity by combination with feselol

Abstract

Urinary bladder cancer is one of the most common cancers worldwide. Human transitional cell carcinoma (TCC) cells are epithelial-like adherent cells originally established from a primary bladder carcinoma. Studies have shown that TCC cells are resistant to some chemotherapeutic agents such as vincristine (VCR). In the present study, the effect of feselol, a sesquiterpene coumarin isolated from the fruits of Ferula badrakema, was investigated on VCR effectiveness. Our results demonstrated that feselol itself did not have any cytotoxic effect on TCC cells. In order to check its combinatorial effects, TCC cells were exposed to various combined concentrations of feselol and VCR. Then, morphological changes were monitored and cytotoxicity was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay for three consequent days. Results showed that the combination of 40 μg/ml VCR with 16 μg/ml feselol increased the cytotoxicity of VCR by 28.32% after 48 h. This effect might be due to inhibition of P-glycoprotein in TCC cells by feselol.

Keywords:

• Ferula badrakema
• sesquiterpene coumarin
• feselol
• vincristine
• TCC cells

Acknowledgements

The authors would like to thank Prof. Javad Behravan for his great advice. We are also grateful to Mrs Zeinab Neshati, Mr Porsa, and Mr Bagherpoure for their excellent technical assistance. This work was supported in part by a grant from Ferdowsi University of Mashhad.