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

Abstract

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.

Validation of Enhancing Effects of Curcumin on Radiotherapy with F98/FGT Glioblastoma-Bearing Rat Model

“…Curcumin, a strong antioxidant and anti-inflammatory agent, has been moved from kitchen to bench examining of its anticancer capacities in aspects of inhibition of cancer initiation, progression, and metastasis [21,31]. In addition to a panel of cancers [21,25,32,33], curcumin is also capable in inhibiting the growth of glioma and glioblastoma cells [34,35]. In literature, curcumin can induce GBM cells to die in forms of autophagy [36] and apoptosis [37].…”

Role of Curcumin and (−)-Epigallocatechin-3-O-Gallate in Bladder Cancer Treatment: A Review

“…Moreover, the complexes studied on C5637 BC cells revealed significant antitumor activity and, in parallel, no antibacterial activity [42,43]. CUR has also been studied in combination with other molecules for the treatment of BC [44,45]. For example, Falke et al [45] proved the dose-dependent antiproliferative effect of the cyclodextrin-CUR complex on human and rat urothelial carcinoma cell lines in vitro, and demonstrated the promising antitumor response after intravesical instillation of the CUR-cyclodextrin complex with and without the BCG vaccine.…”

“…CUR has also been studied in combination with other molecules for the treatment of BC [44,45]. For example, Falke et al [45] proved the dose-dependent antiproliferative effect of the cyclodextrin-CUR complex on human and rat urothelial carcinoma cell lines in vitro, and demonstrated the promising antitumor response after intravesical instillation of the CUR-cyclodextrin complex with and without the BCG vaccine. In another study, Samaddar et al [44] improved the bioavailability of CUR for bladder tumor cells by co-loading it together with anionic plasmid DNA in lipid-coated polyplexes.…”

Molecular Mechanisms of the Anti-Cancer Effects of Isothiocyanates from Cruciferous Vegetables in Bladder Cancer

“…Regarding BC, multiple studies showed that a variety of natural products have anti-cancer effects and maintain quality of life, including Evodia rutaecarpa or curcumin [15,16]. Several reports also demonstrated the relationship between natural products and prevention of carcinogenesis, clinicopathological features, and anti-cancer effects in BC [17,18].…”