Curcumin, but not Prima-1, decreased tumor cell proliferation in the syngeneic murine orthotopic bladder tumor model

Watanabe, Fabio Toshio; Chade, Daher C.; Reis, Sabrina T.; Piantino, Camila Belfort; Oglio, Marcos Francisco Dall; Srougi, Miguel; Leite, Kátia R. M.

doi:10.1590/s1807-59322011001200019

Cited by 24 publications

(15 citation statements)

References 16 publications

(14 reference statements)

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“…We have previously reported a preliminary study evaluating Prima-1 as a potential treatment in an in vivo model of orthotopic urothelial carcinoma. Although this treatment was not effective, there were no side effects, and more studies are necessary to consider this compound as an option in clinical practice (37). …”

Section: Discussionmentioning

confidence: 99%

Prima-1 induces apoptosis in bladder cancer cell lines by activating p53

Piantino¹,

Reis²,

Viana³

et al. 2013

Clinics

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OBJECTIVES:Bladder cancer represents 3% of all carcinomas in the Brazilian population and ranks second in incidence among urological tumors, after prostate cancer. The loss of p53 function is the main genetic alteration related to the development of high-grade muscle-invasive disease. Prima-1 is a small molecule that restores tumor suppressor function to mutant p53 and induces cancer cell death in various cancer types. Our aim was to investigate the ability of Prima-1 to induce apoptosis after DNA damage in bladder cancer cell lines.METHOD:The therapeutic effect of Prima-1 was studied in two bladder cancer cell lines: T24, which is characterized by a p53 mutation, and RT4, which is the wild-type for the p53 gene. Morphological features of apoptosis induced by p53, including mitochondrial membrane potential changes and the expression of thirteen genes involved in apoptosis, were assessed by microscopic observation and quantitative real-time PCR (qRT-PCR).RESULTS:Prima-1 was able to reactivate p53 function in the T24 (p53 mt) bladder cancer cell line and promote apoptosis via the induction of Bax and Puma expression, activation of the caspase cascade and disruption of the mitochondrial membrane in a BAK-independent manner.CONCLUSION:Prima-1 is able to restore the transcriptional activity of p53. Experimental studies in vivo may be conducted to test this molecule as a new therapeutic agent for urothelial carcinomas of the bladder, which characteristically harbor p53 mutations.

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Section: Discussionmentioning

confidence: 99%

Prima-1 induces apoptosis in bladder cancer cell lines by activating p53

Piantino¹,

Reis²,

Viana³

et al. 2013

Clinics

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“…Curcumin is a component of dried turmeric powder, a food spice derived from the plant Curcuma Longa . Curcumin is a nontoxic agent, with anti-inflammatory, antioxidant, and anticarcinogenic activity [ 3 , 4 ], including apoptotic effects on urothelial carcinoma (UC) in vitro [ 5 , 6 ] and in vivo [ 7 – 10 ]. The molecular mechanisms underlying the antitumor effect have not been fully unraveled.…”

Section: Introductionmentioning

confidence: 99%

Curcumin as Treatment for Bladder Cancer: A Preclinical Study of Cyclodextrin-Curcumin Complex and BCG as Intravesical Treatment in an Orthotopic Bladder Cancer Rat Model

Falke

Parkkinen

Vaahtera

et al. 2018

BioMed Research International

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Objective To evaluate the antitumor effect of cyclodextrin-curcumin complex (CDC) on human and rat urothelial carcinoma cells in vitro and to evaluate the effect of intravesical instillations of CDC, BCG, and the combination in vivo in the AY-F344 orthotopic bladder cancer rat model. Curcumin has anticarcinogenic activity on urothelial carcinoma and is therefore under investigation for the treatment of non-muscle invasive bladder cancer. Curcumin and BCG share immunomodulating pathways against urothelial carcinoma. Methods 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 in vitro. For the in vivo experiment, the AY-27 orthotopic bladder cancer F344 rat model was used. Rats were treated with consecutive intravesical instillations of CDC, BCG, the combination of CDC+BCG, or NaCl as control. Results 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. Conclusions Cyclodextrin-curcumin complex showed an antiproliferative effect on human and rat urothelial carcinoma cell lines in vitro. In the aggressive orthotopic bladder cancer rat model, we observed a promising effect of CDC treatment and CDC in combination with BCG.

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“…Electrocautery has been used extensively as a physical means to disrupt the GAG layer [5][6][7][8][9][10][11][12][13] and a protocol demonstrating electrocautery has recently been published in JoVE 14 . However, should an electrocautery unit not be available, chemical means to destroy the GAG layer such as silver nitrate or poly-L-lysine can also be used [15][16][17][18][19][20][21][22][23][24] . Tumors are established effectively by a brief exposure of the bladder to a small volume of silver nitrate (5-10 μl, 0.15-1.0 M, ~10 sec) or longer contact with poly-L-lysine (100 μl of 0.1 mg/ml for 20 min) ( Table 1).…”

Section: Introductionmentioning

confidence: 99%

An Orthotopic Bladder Cancer Model for Gene Delivery Studies

Kasman

Voelkel‐Johnson

2013

JoVE

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Bladder cancer is the second most common cancer of the urogenital tract and novel therapeutic approaches that can reduce recurrence and progression are needed. The tumor microenvironment can significantly influence tumor development and therapy response. It is therefore often desirable to grow tumor cells in the organ from which they originated. This protocol describes an orthotopic model of bladder cancer, in which MB49 murine bladder carcinoma cells are instilled into the bladder via catheterization. Successful tumor cell implantation in this model requires disruption of the protective glycosaminoglycan layer, which can be accomplished by physical or chemical means. In our protocol the bladder is treated with trypsin prior to cell instillation. Catheterization of the bladder can also be used to deliver therapeutics once the tumors are established. This protocol describes the delivery of an adenoviral construct that expresses a luciferase reporter gene. While our protocol has been optimized for short-term studies and focuses on gene delivery, the methodology of mouse bladder catheterization has broad applications.

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Curcumin, but not Prima-1, decreased tumor cell proliferation in the syngeneic murine orthotopic bladder tumor model

Cited by 24 publications

References 16 publications

Prima-1 induces apoptosis in bladder cancer cell lines by activating p53

Prima-1 induces apoptosis in bladder cancer cell lines by activating p53

Curcumin as Treatment for Bladder Cancer: A Preclinical Study of Cyclodextrin-Curcumin Complex and BCG as Intravesical Treatment in an Orthotopic Bladder Cancer Rat Model

An Orthotopic Bladder Cancer Model for Gene Delivery Studies

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