Neoplasma Vol.52, p.510-516, 2005
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Title: Enhanced sensitivity of human ovarian carcinoma cell lines A2780 and A2780/CP to the combination of cisplatin and synthetic isothiocyanate ethyl 4-isothiocyanatobutanoate
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Author: J., BODO
; J., CHOVANCOVA
; L., HUNAKOVA
; J., SEDLAK
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Abstract: Naturally occurring and synthetic isothiocyanates (ITCs) are known
as chemopreventive agents. The present study shows
a new synthetic ITC derivate ethyl 4-isothiocyanatobutanoate (E-
4IB) as an effective modulator of cellular proliferation and
inducer of apoptosis with potential utility as an anticancer drug,
as well as a sensitizer to routinely used chemotherapeutic
agent cisplatin (cis-Pt).
Evaluation of the growth inhibitory effects of E-4IB 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 was performed.
Effect of E-4IB was assessed both alone and in paired combination
with cisplatin. Combination index (CI) values from
Calcusyn software were used to characterize the interactions as
synergistic, additive, or antagonistic. Significant synergistic
effect in growth inhibition of E-4IB (0.5–5 µM) with cis-Pt (2.5–10 µM) on A2780 parental cell line (CI from 0.39 to 0.75)
was also observed on A2780/CP resistant subline, although to a
lesser extent (CI from 0.43 to 0.86) for cis-Pt concentrations
5–25 µM and the same concentrations of E-4IB. Synergy in growth
inhibition correlated with the potential of E-4IB to stimulate
apoptosis induced by cis-Pt (from 9.5% to 24.7% at 24 hours) while
E-4IB alone induced 3.6% of apoptotic cells in
A2780 cell line.
We conclude that E-4IB may be worth of further studies assessing
its value in the ovarian carcinoma treatment, in combination
with the other chemotherapeutic agents.
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Keywords: ovarian carcinoma, isothiocyanate, cisplatin, growth inhibition,
apoptosis
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Year: 2005, Volume: 52, Issue: |
Page From: 510, Page To: 516 |
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