A Randomized Double-Blind Placebo-Controlled Phase IIB Trial of Curcumin in Oral Leukoplakia.

Oral leukoplakia is a potentially malignant lesion of the oral cavity, for which no effective treatment is available. We investigated the effectiveness of curcumin, a potent inhibitor of NF-κB/COX-2, molecules perturbed in oral carcinogenesis, to treat leukoplakia. Subjects with oral leukoplakia (n = 223) were randomized (1:1 ratio) to receive orally, either 3.6 g/day of curcumin (n = 111) or placebo (n = 112), for 6 months. The primary endpoint was clinical response obtained by bi-dimensional measurement of leukoplakia size at recruitment and 6 months. Histologic response, combined clinical and histologic response, durability and effect of long-term therapy for an additional six months in partial responders, safety and compliance were the secondary endpoints. Clinical response was observed in 75 (67.5%) subjects [95% confidence interval (CI), 58.4-75.6] in the curcumin and 62 (55.3%; 95% CI, 46.1-64.2) in placebo arm (P = 0.03). This response was durable, with 16 of the 18 (88.9%; 95% CI, 67.2-96.9) subjects with complete response in curcumin and 7 of 8 subjects (87.5%) in placebo arm, demonstrating no relapse after 6 months follow-up. Difference in histologic response between curcumin and placebo was not significant (HR, 0.88, 95% CI, 0.45-1.71; P = 0.71). Combined clinical and histologic response assessment indicated a significantly better response with curcumin (HR, 0.50; 95% CI, 0.27-0.92; P = 0.02). Continued therapy, in subjects with partial response at 6 months, did not yield additional benefit. The treatment did not raise any safety concerns. Treatment of oral leukoplakia with curcumin (3.6 g for six months), thus was well tolerated and demonstrated significant and durable clinical response for 6 months. Cancer Prev Res; 9(8); 683-91. ©2016 AACR.

Extract from Serenoa repens suppresses the invasion activity of human urological cancer cells by inhibiting urokinase-type plasminogen activator.

We used three human urological cancer cell lines, PC-3, LNCaP and SKRC-1, to investigate the effects of the extract from Serenoa repens (Palmae) on tumor cell invasion. The invasion activity of these cell lines was determined in vitro using a Transwell cell-culture chamber. The invasion activity of PC-3 cells into Matrigel was effectively suppressed by the extract at the concentration range of 1-10 microg/ml, while that of LNCaP and SKRC-1 cells was unaffected by the extract. The extract did not affect the viability, adhesion ability, or motility of the cell lines. uPA is more strongly expressed on the membrane fraction of PC-3 cells than that of LNCaP or SKRC-1 cells. The purified uPA activity is inhibited by the extract from S. repens in a dose-dependent manner, suggesting that the suppression of PC-3 cell invasion by the extract is based on an inhibition of the uPA activity which is necessary for tumor cell invasion. These data suggest that the extract from S. repens specifically inhibits the uPA activity and may therefore be useful for the therapeutic treatment of prostate cancer.