Chemopreventive Synergism between Green Tea Extract and Curcumin in Patients with Potentially Malignant Oral Disorders: A Double-blind, Randomized Preliminary Study

Aim: The aim of the study was to assess the synergistic effect of green tea extract and curcumin in patients with oral potentially malignant disorders (OPMDs) and to ascertain the mechanism of action of these chemopreventive agents through assessment of suitable biomarkers.

Materials and methods: Subjects with OPMDs (n = 60) were randomized to receive green tea extract [topical + systemic (800 mg/day)] or curcumin [topical + Systemic (950 mg/day)] or a combination therapy with 20 patients in each group for 3 months. Biomarkers (Ki67, cyclin D1, and p53) were evaluated in baseline and 12-week biopsies.

Results: The clinical response rate observed in OPMDs was higher in the combination group (n = 13; 65%) as compared to the curcumin (n = 11; 55%) and the green tea extract group (n = 7; 35%) and was statistically highly significant. Treatment medications also improved histological grades, although not statistically significant. All the study drugs were well tolerated by patients and did not raise any safety concerns. There was statistically significant (p < 0.01) downregulation of p53, Ki67, and cyclin D1 expression at 3 months as compared to baseline in the combination group.

Conclusion: Treatment of OPMDs with curcumin and green tea extract combination demonstrated a significant clinical response supported by downregulation of molecular biomarkers in the short-term (12 weeks). The present results warrant a long-term clinical testing of green tea and curcumin combination for oral cancer prevention.

Clinical significance: Chemoprevention is a promising treatment strategy to reverse, stabilize, or arrest progression of these OPMDs. Use of natural dietary agents like green tea and curcumin, which are readily available, have low toxicity, and more importantly demonstrate a synergistic effect, is an attractive alternative in the chemoprevention of oral cancer. The assessment of biomarkers has helped us to understand the mechanism of action of these chemopreventive agents.