The Novel Platinum Analog Dicycloplatin Provides Reliable Growth Inhibition of Urothelial Carcinoma Cells In Vitro

• Published in: Anticancer research Vol. 44; no. 8; pp. 3243 - 3254
• Main Authors: Zekan, David, Hogan, Thomas, Jackson, Barbara, Jackson, Garrett, Kandzari, Stanley
• Format: Journal Article
• Language: English
• Published: Athens International Institute of Anticancer Research 01.08.2024
• Subjects: Bladder; Cancer; Carboplatin; Cisplatin; Effectiveness; Exposure; In vitro methods and tests; Oxaliplatin; Platinum; Time dependence; Tumor cell lines; Urothelial carcinoma
• ISSN: 0250-7005; 1791-7530; 1791-7530
• DOI: 10.21873/anticanres.17142

Background/Aim: Platinum-based chemotherapies are a component of standard-of-care regimens for urothelial carcinoma (UC). These nephrotoxic drugs are often dose-limiting, with cisplatin and carboplatin being the most commonly used. Dicycloplatin (DCP) has better solubility and stability, with comparable efficacy and better tolerability. Some suggest the use of DCP as primary treatment for non-muscle-invasive bladder cancer. We exposed UC cell lines to DCP in vitro to assess its efficacy. Materials and Methods: A high grade (IV) in vitro UC cell line (TCCSUP) was exposed to varying concentrations of cisplatin (0-600 μg/ml), carboplatin (0-600 μg/ml), oxaliplatin (0-4.0 μg/ml), and DCP (0-350 μg/ml). Grade II-IV cells were exposed to varying concentrations of DCP (0-350 μg/ml) to assess time- and concentration-dependent growth inhibition, and simulate intravesical treatment. Growth inhibition was determined following 24, 48, and 72 h of exposure, using a tetrazolium dye to assess mitochondrial dehydrogenase activity. Results: DCP, cisplatin, and carboplatin effectively achieved >90% cell kill at 72 h. Concentrations of 325 μg/ml DCP, 50 μg/ml cisplatin, and 600 μg/ml carboplatin were sufficient for >90% cell-kill, with cisplatin demonstrating the highest efficacy at the lowest concentration/time intervals. Dose- and time-dependent cell kill were demonstrated at varying concentrations of DCP in grade II-IV cell lines, including cells exposed intravesically. Conclusion: In vitro, DCP demonstrates cell-killing efficacy in a time- and concentration-dependent manner in grade II-IV UC cell lines, showing promise for its intravenous, oral, and intravesical use for bladder UC in both primary and adjuvant/neoadjuvant settings.