Quantitation of chemopreventive synergism between (-)-epigallocatechin-3-gallate and curcumin in normal, premalignant and malignant human oral epithelial cells Journal Article

  

Authors:	Khafif, A.; Schantz, S. P.; Chou, T. C.; Edelstein, D.; Sacks, P. G.
Article Title:	Quantitation of chemopreventive synergism between (-)-epigallocatechin-3-gallate and curcumin in normal, premalignant and malignant human oral epithelial cells
Abstract:	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.
Keywords:	controlled study; human tissue; squamous cell carcinoma; drug potentiation; flow cytometry; cells, cultured; cell cycle; cancer prevention; chemoprophylaxis; cancer cell culture; dose-response relationship, drug; cancer model; drug synergism; cancer inhibition; anticarcinogenic agents; epithelial cells; epigallocatechin gallate; mouth mucosa; mouth neoplasms; mouth cancer; curcumin; leukoplakia; precancerous conditions; tea; precancer; mitosis inhibition; catechin; humans; human; priority journal; article
Journal Title:	Carcinogenesis
Volume:	19
Issue:	3
ISSN:	0143-3334
Publisher:	Oxford University Press
Date Published:	1998-03-01
Start Page:	419
End Page:	424
Language:	English
DOI:	10.1093/carcin/19.3.419
PUBMED:	9525275
PROVIDER:	scopus
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0031927214&doi=10.1093%2fcarcin%2f19.3.419&partnerID=40&md5=774aaa64ab67c9c804482568b625cd0c
Notes:	Article -- Export Date: 12 December 2016 -- Source: Scopus

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