Differential response of normal, premalignant and malignant human oral epithelial cells to growth inhibition by chemopreventive agents.
Squamous cell carcinoma (SCC) of the oral cavity is a multistep process, progressing through a series of discrete, irreversible and complementary alterations in genes that control cell growth, death, and differentiation. In the premalignant state, the oral mucosa progresses through various grades of epithelial dysplasia, with the potential to convert to SCC. Chemopreventive strategies are designed to suppress, reverse, or prevent the formation of premalignant lesions and their subsequent progression to SCC. In the present study, we determined the growth inhibitory effect of 21 chemopreventive agents in a cell culture model using normal, premalignant, and malignant human oral mucosal cell lines. There were significant differences in the growth inhibitory responses of these cell lines to selected retinoids and non-retinoid analogs. Among the retinoids tested, the synthetic retinamides, as a class, showed selective growth inhibition of both premalignant and malignant cells compared to normal human oral epithelial cells in culture. Within the retinamide class, 2CPR exhibited the greatest selectivity in the growth inhibition of premalignant and malignant cells. Among the non-retinoids analyzed, DFMO was a moderate to potent inhibitor of malignant and premalignant oral cell growth, respectively, and stimulated normal oral cell growth at low concentrations. Using this in vitro approach, we have identified several potential chemopreventive agents for oral cancer as selective growth inhibitors of premalignant ahd malignant human oral mucosa cells.
D'Ambrosio
S M
SM
Ohio State University School of Medicine and Public Health, Columbus, USA. dambrosio.1@osu.edu
Gibson-D'Ambrosio
R
R
Milo
G E
GE
Casto
B
B
Kelloff
G J
GJ
Steele
V E
VE
D000111:Acetylcysteine / Q000494:pharmacology; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003474:Curcumin / Q000494:pharmacology; D000518:Eflornithine / Q000494:pharmacology; D006801:Humans; D009061:Mouth Mucosa / Q000187:drug effects*; D009062:Mouth Neoplasms / Q000473:pathology / Q000517:prevention & control*; D011230:Precancerous Conditions / Q000473:pathology / Q000517:prevention & control*; D012176:Retinoids / Q000494:pharmacology
D016588:Anticarcinogenic Agents; D012176:Retinoids; D003474:Curcumin; D000111:Acetylcysteine; D000518:Eflornithine