Effects of Curcumin in an Orthotopic Murine Bladder Tumor Model

Cigarette smoking (CS) is the main risk factor for bladder cancer development. There are more than 100 carcinogens and metastasis. Curcumin is a polyphenol compound derived from Curcuma longa that suppress cellular study was to assess the effects of curcumin in bladder urothelial carcinoma. We studied the effects of curcumin in vitro


INTRODUCTION
this animal model of bladder cancer.

Tumor Cell Line
The murine transitional cell carcinoma cell -ics.

Orthotopic Tumor Implantation
were administered general anesthesia with i.p. injecthrough the urethra into the bladder using an inert lubricant (sterile contact gel).In order to prepare the the bladder wall was made by intravesical instillation -5 viable tumor cells was instilled into the bladder.

Curcumin Treatment
Twenty-four hours following tumor implanta-ated.Mice were randomly assigned to either a control be studied.The curcumin doses used were 100 μM received the curcumin with no previous induction of in the bladder mucosa.

Assessment of Tumor
The mice were evaluated on a daily basis inhalation.The bladder was resected and weighed without urine or blood.

Histopathology Analysis
-Tumors were measured under the microscope using invasion into the bladder wall were recorded for pathologist.

Immunohistochemistry
Three-micrometer sections from the paraf-pattern of staining.

Statistical Analysis
Statistical analyses were performed by using and range.We used the Student's-t-test or the Mann-Whitney test for the evaluation of numerical variables

In Vitro Studies
-μM of curcumin lost their elongated shape and had vacuoles in the cytoplasm.

In Vivo Studies
There was no statistical difference between the two groups with regards to changes in body weight.The mean weight of the animals at the be-th with intravesical curcumin.This difference was also The median bladder weight of control animals difference for this parameter between the groups (p There was a statistical difference between the There were no differences in the degree of necrosis or level of invasion of the neoplasia for the of treated mice.There was no statistical difference Four animals with no tumors were treated with curcumin to show the effect of the substance in the observed in the lamina propria or in the muscle wall.

Immunohistochemical Expression of Cyclin D1, Bcl2 and Cox-2
in only one case of the group of treated animals (p differences between the groups.through tumor cells in vitro and causes a decrease in tumor could be an option for treatment of bladder cancer.is a disadvantage in its use as a treatment for cancer.already been shown to be able to inhibit proliferation istered when curcumin has been used as an adjuvant

Curcumin is a polyphenol compound derived
The standard of care in the treatment of noninvasive bladder cancer (pTa) or tumors compromising the lamina propria (pT1) is transurethral resection sive muscle or metastatic bladder cancer has also been successful in the treatment of bladder cancer; consethat could be used to treat this neoplasia.
Cigarette smoking is the most important risk has already been shown that carcinogenic substances proangiogenic factors associated with aggressive tumor growth.
cumin mediates its activity in a dose-depen-

EDITORIAL COMMENT
This is an interesting proof of concept study looking at the role of intravesical curcumin in the management of bladder cancer.Cigarette smoking is may be downregulated by curcumin.
This study has proven the ability to develop an in vivo clinical model for muscle invasive bladder remains speculative.
gene products in IFN-alpha-sensitive and IFN-alpharesistant human bladder cancer cells.Mol Cancer Ther. -

Accepted after revision:
July 6, 2009 --plicable to the usual type of bladder cancer we would CIS or high grade T1 lesions.
mended for their efforts and the success of their in invasive bladder cancer.

Dr. Mark Frydenberg
malignancy in the United States.Progression and multifocality (1).The use of tobacco is one of the main causes of bladder cancer due to the presence of thousands of different -Basic and Translational Urology Basic and Translational Urology the potential mediators of CS-induced alterations is has been implicated in chemical carcinogenesis and proteins that are responsible for the transcription of lowed by intravesical instillation of bacillus Calmette-they have no impact on long-term survival or disease --Syngeneic animal models are often used to used the syngeneic orthotopic murine bladder cancer induced bladder cancer into syngeneic immunocomconsidering its ability to mimic intravesical condiresponse to drugs in an immunocompetent host (11).
already described by Chade et al. versity of Sao Paulo and maintained at our animal care facility for one week prior to use.The mice were the institution's ethical board council.

Figure 1 -
Figure 1 -Columns show the percentage of viable bladder tumor cells when exposed to variable concentrations of curcumin.At 50 mM, there was 55% of apoptosis; in levels higher than 100 mM, less than 10% of tumor cells remained viable.

Figure 2 -
Figure 2 -Photomicrography of the MB49 bladder tumor cell culture exposed to variable concentration of curcumin, showing progressive apoptosis.In concentrations above 100 mM there are no viable cells.

Figure 3 -
Figure 3 -Photomicrography, hematoxylin and eosin-stained slide showing an invasive orthotopic urothelial bladder tumor in the bladder wall with a great amount of necrosis.The statistical submitted to curcumin treatment.

Figure 4 -
Figure 4 -A) Immunohistochemistry study of strong and diffuse expression of Cyclin D1 in the nuclei of tumor cells.Tumors from mice submitted to curcumin instillation showed a mean reduction of 13% in Cyclin expression in comparison with control animals.-