Cancer Research Institute, Bratislava, Slovak Republic.
Neoplasma. 2010;57(5):473-81. doi: 10.4149/neo_2010_05_473.
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 (CI) values from Calcusyn software were used to characterize the interactions of homoITC and cis-Pt as synergistic (CI1). Significant synergistic effect in growth inhibition of homoITC (5 - 15 microM) and cis-Pt (2.5 - 10 microM) 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 microM 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.
异硫氰酸酯(ITC)是十字花科蔬菜中常见的化学预防剂,在体外对癌细胞系具有生长抑制和诱导凋亡的作用。我们的研究提出了一种新的合成 ITC 衍生物吲哚-3-乙基异硫氰酸酯(homoITC),作为一种有效的细胞增殖调节剂和凋亡诱导剂,具有作为抗癌药物或常规化疗药物顺铂(cis-Pt)增敏剂的潜在用途。
我们使用 MTT 试验分析 homoITC 在人卵巢癌细胞系 A2780 及其顺铂耐药变体 A2780/CP 中的生长抑制作用及其诱导凋亡的特性通过流式细胞术和 caspase 3 激活。Calcusyn 软件中的组合指数(CI)值用于表征 homoITC 和 cis-Pt 的相互作用作为协同作用(CI1)。在 A2780 亲本细胞系中, homoITC(5-15 μM)和 cis-Pt(2.5-10 μM)对生长的显著协同抑制作用(CI 从 0.42 到 0.85)也观察到在 A2780/CP 耐药亚系中(CI 从 0.18 到 0.73)对于 10-50 μM cis-Pt 浓度和相同浓度的 homoITC。生长抑制的协同作用与 homoITC 刺激 cis-Pt 诱导的凋亡的潜力相关。我们得出结论,homoITC 可能值得进一步研究,以评估其在卵巢癌治疗中的价值,并阐明其作用机制。