Carcinogenesis, Vol 19, 419-424, Copyright © 1998 by Oxford University Press
A Khafif, SP Schantz, TC Chou, D Edelstein and PG Sacks
An in vitro model for oral cancer was used to examine the growth inhibitory
effects of chemopreventive agents when used singly and in combination. The
model consists of primary cultures of normal oral epithelial cells, newly
established cell lines derived from dysplastic leukoplakia and squamous
cell carcinoma. Two naturally occurring substances,
(-)-epigallocatechin-3-gallate (EGCG) from green tea and curcumin from the
spice turmeric were tested. Cells were treated singly and in combination
and effects on growth determined in 5-day growth assays and by cell cycle
analysis. Effective dose 50s and the combination index were calculated with
the computerized Chou-Talalay method which is based on the median-effect
principle. Agents were shown to differ in their inhibitory potency. EGCG
was less effective with cell progression; the cancer cells were more
resistant than normal or dysplastic cells. In contrast, curcumin was
equally effective regardless of the cell type tested. Cell cycle analysis
indicated that EGCG blocked cells in G1, whereas curcumin blocked cells in
S/G2M. The combination of both agents showed synergistic interactions in
growth inhibition and increased sigmoidicity (steepness) of the dose-effect
curves, a response that was dose and cell type dependent. Combinations
allowed for a dose reduction of 4.4-8.5-fold for EGCG and 2.2-2.8-fold for
curcumin at ED50s as indicated by the dose reduction index (DRI). Even
greater DRI values were observed above ED50 levels. Our results demonstrate
that this model which includes normal, premalignant and malignant oral
cells can be used to analyse the relative potential of various
chemopreventive agents. Two such naturally-occurring agents, EGCG and
curcumin, were noted to inhibit growth by different mechanisms, a factor
which may account for their demonstrable interactive synergistic effect.
ARTICLES
Quantitation of chemopreventive synergism between (-)-epigallocatechin- 3-gallate and curcumin in normal, premalignant and malignant human oral epithelial cells
Department of Surgery, Head and Neck Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
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