Augmented efficacy of uttroside B over sorafenib in a murine model of human hepatocellular carcinoma

Abstract

BackgroundWe previously reported the potency of S. nigrum-derived uttroside B (Utt-B). Recently Utt-B is flagged as an ‘orphan drug’ against hepatocellular carcinoma (HCC) by the US FDA. The current study aims to validate the enhanced in vivo efficacy of Utt-B over sorafenib, the first-line treatment option against HCC.MethodsHuman liver cancer cell line, HepG2 was employed as an HCC model and the comparison between Utt-B vs sorafenib therapeutic efficacies against HCC in vivo were evaluated in NOD.CB17-Prkdcscid/J mice that bear HepG2-induced HCC xenografts.ResultsOur data indicate that Utt-B is a more potent anti-HCC drug than sorafenib, in vivo. Apart from the superior therapeutic benefit over sorafenib, Utt-B is pharmacologically safer in vivo, and owing to this virtue, the drug-induced side effects are largely alleviated in the context of HCC chemotherapy.ConclusionsOur data demonstrate the superior therapeutic index of Utt-B over sorafenib against HCC. Clinical studies in HCC patients utilizing Utt-B, which now holds the US FDA approval as an ‘orphan drug’, is an essential step to promote this drug from bench to bedside.