curcumin and Carcinoma--Transitional-Cell

Topics: Administration, Intravesical; Animals; Carcinoma, Transitional Cell; Curcumin; Cyclodextrins; Rats; Urinary Bladder Neoplasms

To evaluate the antitumor effect of cyclodextrin-curcumin complex (CDC) on human and rat urothelial carcinoma cells. Curcumin was complexed with cyclodextrin to improve solubility. Four human urothelial carcinoma cell lines and the AY-27 rat cell line were exposed to various concentrations of CDC. CDC showed a dose-dependent antiproliferative effect on all human urothelial carcinoma cell lines tested and the rat AY-27 urothelial carcinoma cell line. Moreover, intravesical treatment with CDC and CDC+BCG results in a lower percentage of tumors (60% and 68%, respectively) compared to BCG (75%) or control (85%). This difference with placebo was not statistically significant (p=0.078 and 0.199, respectively). However, tumors present in the placebo and BCG-treated rats were generally of higher stage.. Cyclodextrin-curcumin complex showed an antiproliferative effect on human and rat urothelial carcinoma cell lines

Topics: Animals; BCG Vaccine; Carcinoma, Transitional Cell; Curcumin; Cyclodextrins; Humans; Rats; Rats, Inbred F344; Urinary Bladder Neoplasms

Transitional cell carcinoma (TCC) of the urinary bladder is the most common cancer of the urinary tract. Most of the TCC cases are of the superficial type and are treated with transurethral resection (TUR). However, the recurrence rate is high and the current treatments have the drawback of inducing strong systemic toxicity or cause painful cystitis. Therefore, it would be of therapeutic value to develop novel concepts and identify novel drugs for the treatment of bladder cancer. Ki-67 is a large nucleolar phosphoprotein whose expression is tightly linked to cell proliferation, and curcumin, a phytochemical derived from the rhizome Curcuma longa, has been shown to possess powerful anticancer properties. In this study, we evaluated the combined efficacy of curcumin and a siRNA against Ki-67 mRNA (Ki-67-7) in rat (AY-27) and human (T-24) bladder cancer cells. The anticancer effects were assessed by the determination of cell viability, apoptosis and cell cycle analysis. Ki-67-7 (10 nM) and curcumin (10 µM), when treated independently, were moderately effective. However, in their combined presence, proliferation of bladder cancer cells was profoundly (>85%) inhibited; the rate of apoptosis in the combined presence of curcumin and Ki-67-7 (36%) was greater than that due to Ki-67-7 (14%) or curcumin (13%) alone. A similar synergy between curcumin and Ki-67-7 in inducing cell cycle arrest was also observed. Western blot analysis suggested that pretreatment with Ki-67-7 sensitized bladder cancer cells to curcumin-mediated apoptosis and cell cycle arrest by p53- and p21-independent mechanisms. These data suggest that a combination of anti-Ki-67 siRNA and curcumin could be a viable treatment against the proliferation of bladder cancer cells.

Topics: Animals; Antineoplastic Agents; Apoptosis; Carcinoma, Transitional Cell; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Curcumin; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; Humans; Ki-67 Antigen; Rats; Ribonuclease III; RNA Interference; RNA, Small Interfering; Signal Transduction; Urinary Bladder Neoplasms

The development of an effective nontoxic intravesical agent that may be used immediately after bladder tumor resection to prevent the implantation of tumor cells would be a significant clinical advancement. We report the cytotoxic effects of curcumin on bladder tumor cell lines as well as its effects on the intravesical implantation of tumor cells in C3H mice.. UMUC human and MBT-2 mouse bladder cancer lines were incubated with 0 to 100 microM. curcumin in dimethyl sulfoxide for 30 minutes and cell viability was determined by clonal assay. Additional culture dishes were incubated with curcumin and processed for electron microscopy. Using the C3H mice and the MBT2 tumor lines the effects of intravesical curcumin on tumor implantation after bladder injury was studied. The 10 group 1 mice served as nontreatment controls. In the 18 group 2 mice 30 minutes after tumor cell implantation 100 microM. curcumin in 0.1% dimethyl sulfoxide were instilled intravesically for 30 minutes. The 15 group 3 mice served as treatment controls with 0.1% dimethyl sulfoxide or culture medium instilled intravesically for 30 minutes. Animals were sacrificed 7 to 10 days after treatment and the bladder was subjected to histological analysis for tumor.. At the 100 microM. dose curcumin was completely lethal to the 2 cell lines on clonal growth assay. Electron microscopy revealed apoptotic bodies after curcumin administration. The tumor implantation rate was 16.7% (3 of 18 mice) in curcumin treated bladders and 73% (11 of 15) in the vehicle control group.. At the 100 microm. concentration curcumin is a potent cytotoxic agent against the MBT and UMUC bladder tumor cell lines. In addition, curcumin effectively inhibits tumor implantation and growth in this murine bladder tumor model.

Topics: Animals; Antineoplastic Agents; Carcinoma, Transitional Cell; Cell Adhesion; Curcumin; Mice; Mice, Inbred C3H; Microscopy, Electron; Tumor Cells, Cultured; Urinary Bladder Neoplasms