title: Chondroitin sulphate enhances the antitumor activity of gemcitabine             and mitomycin-C in bladder cancer cells with different mechanisms.
abstract: Non-muscle invasive bladder cancer is the most common type of bladder cancer             in Western countries. The glycosaminoglycan (GAG) layer at the bladder surface             non-specifically blocks the adherence of bacteria, ions and molecules to the bladder             epithelium and bladder cancer cells express CD44 that binds GAG. Currently, there             are few options other than cystectomy for the management of non-muscle invasive             bladder cancer with intravesical chemotherapy using several drugs such as gemcitabine             (GEM) and mitomycin-C (MMC) with poor prophylactic activity. In this study, we             investigated the effects of the GAG chondroitin sulphate (CS) on the growth inhibition             of human bladder cancer cell lines HT-1376 and effects of the combination between             GEM or MMC with CS. We have found that CS, MMC and GEM induced 50% growth inhibition             at 72 h. Therefore, we have evaluated the growth inhibition induced by different             concentration of CS in combination with MMC or GEM, respectively, at 72 h. We             have observed, at Calcusyn analysis, a synergism when HT-1376 cells were treated             with CS in combination with MMC or GEM, respectively, if used at an equimolar             ratio. We have also found that CS/GEM combination induced a strong potentiation             of apoptosis with the consequent activation of caspases 9 and 3. On the other             hand, HT-1376 cells were necrotic if exposed to the CS/MMC combination and no             signs of caspase activation was observed. In conclusion, in the human bladder             cancer cell line HT-1376 pharmacological combination of CS with GEM or MMC resulted             in a strong synergism on cell growth inhibition.
authors: Department of Urology, University Federico II, Naples, Italy.
authors: Matteo
authors: M
authors: Ferro
authors: Gaia
authors: G
authors: Giuberti
authors: Silvia
authors: S
authors: Zappavigna
authors: Sisto
authors: S
authors: Perdonà
authors: Gaetano
authors: G
authors: Facchini
authors: Pasquale
authors: P
authors: Sperlongano
authors: Stefania
authors: S
authors: Porto
authors: Giuseppe
authors: G
authors: Di Lorenzo
authors: Carlo
authors: C
authors: Buonerba
authors: Alberto
authors: A
authors: Abbruzzese
authors: Vincenzo
authors: V
authors: Altieri
authors: Michele
authors: M
authors: Caraglia
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002809:Chondroitin Sulfates / Q000494:pharmacology* / Q000627:therapeutic use; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D016685:Mitomycin / Q000494:pharmacology* / Q000627:therapeutic use; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D016685:Mitomycin; D002809:Chondroitin Sulfates; D020169:Caspases; D000093542:Gemcitabine