Synthetic isothiocyanate indole-3-ethyl isothiocyanate (homoITC) enhances sensitivity of human ovarian carcinoma cell lines A2780 and A2780/CP to cisplatin

Isothiocyanates (ITCs), popular chemopreventive agents present in cruciferous vegetables, prove growth-inhibiting and apoptosis-inducing activities in cancer cell lines in vitro. Our study presents a new synthetic ITC derivate indol-3-ethyl isothiocyanate (homoITC) as an effective modulator of cellular proliferation and inducer of apoptosis with potential utility as an anticancer drug or a sensitizer to routinely used chemotherapeutic agent cisplatin (cis-Pt). We analyzed the growth inhibitory effects of homoITC in the human ovarian carcinoma cell line A2780 and its cisplatin-resistant variant A2780/CP using MTT-test and its apoptosis-inducing properties by flow cytometry and caspase 3 activation. Combination index (Cl) values from Calcusyn software were used to characterize the interactions of homoITC and cis-Pt as synergistic (CI<1), additive (CI=1), or antagonistic (CI>1). Significant synergistic effect in growth inhibition of homoITC (5 - 15 mu M) and cis-Pt (2.5 - 10 mu M) on A2780 parental cell line (CI from 0.42 to 0.85) was also observed on A2780/CP resistant subline (CI from 0.18 to 0.73) for 10-50 mu M cis-Pt concentrations and the same concentrations of homoITC. Synergy in growth inhibition correlated with the potential of homoITC to stimulate apoptosis induced by cis-Pt. We conclude that homoITC may be worth of further studies assessing its value in the ovarian cancer treatment and elucidating mechanisms of its action.