Objective: Esophageal Squamous Cell Carcinoma (ESCC) is one of the most common cancers in Iran, and its incidence in Iranian population is 20 times more than industrial countries. Despite advances in cancer management and therapy, survival rate of ESCC still remains low, partially due to the presence of stem-like cancer cells with rapid growth, chemotherapy resistance and metastatic potential. In current study, synergic effect of auraptene, a natural coumarin derivative, on cisplatin cytotoxicity has been investigated in KYSE30 cells, a stem-like ESCC cell line. Materials and Methods: Auraptene was extracted from Citrus species using silica gel column chromatography and its structure was confirmed by nuclear magnetic resonance spectra. Viability of KYSE30 and HFF3 cells, human normal fibroblasts, was evaluated by thiazolyl blue tetrazolium bromide during 4 consecutive days. Apoptosis was assessed flow cytometrically using FITC annexin V apoptosis detection kit with propidium iodide. Results: Auraptene had no significant toxic effect on KYSE30 and HFF3 cells in 10, 20 and 40 μg/ml after 24, 48, 72 and 96 h. To examine auraptene effect on cisplatin cytotoxicity, KYSE30 cells were treated with various combining concentrations, including 5, 10 and 20 μg/ml auraptene with 1, 2 and 4 μg/ml cisplatin. Results revealed that combination of 20 μg/ml auraptene with 1 μg/ml cisplatin increased the toxicity of cisplatin after 72 h by 31.5%. Apoptosis assay confirmed morphological observations and MTT results as apoptosis induced by cisplatin in KYSE30 cells was enhanced by 34.7% when used in combination with auraptene. Conclusion: Since non-toxic concentration of auraptene increases the cytotoxicity of cisplatin by more than 30%, this coumarin could be considered as a suitable candidate for future in vivo and clinical studies.

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