Ovarian and
pancreatic cancers are two of the most aggressive and lethal
cancers, whose management faces only limited therapeutic options. Typically, these
tumors spread insidiously accompanied first with atypical symptoms, and usually shift to a drug resistance phenotype with the current
pharmaceutical armamentarium. Thus, the development of new drugs acting via a different mechanism of action represents a clear priority. Herein, we are reporting for the first time that the aminosteroid derivative RM-133, developed in our laboratory, displays promising activity on two models of aggressive
cancers, namely ovarian (OVCAR-3) and pancreatic (PANC-1)
cancers. The IC50 value of RM-133 was 0.8 μM and 0.3 μM for OVCAR-3 and PANC-1 cell lines in culture, respectively. Based on pharmacokinetic studies on RM-133 using 11 different vehicles, we selected two main vehicles: aqueous 0.4%
methylcellulose:
ethanol (92:8) and
sunflower oil:
ethanol (92:8) for in vivo studies. Using
subcutaneous injection of RM-133 with the
methylcellulose-based vehicle, growth of PANC-1
tumors xenografted to nude mice was inhibited by 63%. Quite interestingly, RM-133 injected subcutaneously with the
methylcellulose-based or sunflower-based vehicles reduced OVCAR-3 xenograft growth by 122% and 100%, respectively. After the end of RM-133 treatment using the
methylcellulose-based vehicle, OVCAR-3
tumor growth inhibition was maintained for ≥ 1 week. RM-133 was also well tolerated in the whole animal, no apparent sign of toxicity having been detected in the xenograft studies.