Abstract |
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).<br />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.
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Authors | P Stehlik, H Paulikova, L Hunakova |
Journal | Neoplasma
(Neoplasma)
Vol. 57
Issue 5
Pg. 473-81
( 2010)
ISSN: 0028-2685 [Print] Slovakia |
PMID | 20568902
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Isothiocyanates
- indole-3-ethyl isothiocyanate
- Cisplatin
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Topics |
- Antineoplastic Agents
(pharmacology)
- Apoptosis
(drug effects)
- Cell Cycle
(drug effects)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Cisplatin
(pharmacology)
- Drug Resistance, Neoplasm
- Drug Synergism
- Female
- Flow Cytometry
- Humans
- Isothiocyanates
(pharmacology)
- Ovarian Neoplasms
(drug therapy, pathology)
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