Abstract:
We previously reported the remarkable potency of uttroside B (Utt-B), saponin-isolated and
characterized in our lab from Solanum nigrum Linn, against HCC. Recently, the U.S. FDA approved
Utt-B as an ‘orphan drug’ against HCC. The current study validates the superior anti-HCC efficacy
of Utt-B over sorafenib, the first-line treatment option against HCC. The therapeutic efficacies of
Utt-B vs. sorafenib against HCC were compared in vitro, using various liver cancer cell lines and
in vivo, utilizing NOD.CB17-Prkdcscid/J mice bearing human HCC xenografts. Our data indicate
that Utt-B holds an augmented anti-HCC efficacy over sorafenib. Our previous report demonstrated
the pharmacological safety of Utt-B in Chang Liver, the normal immortalized hepatocytes, and in
the acute and chronic toxicity murine models even at elevated Utt-B concentrations. Here, we show
that higher concentrations of sorafenib induce severe toxicity, in Chang Liver, as well as in acute and
chronic in vivo models, indicating that, apart from the superior therapeutic benefit over sorafenib,
Utt-B is a pharmacologically safer molecule, and the drug-induced undesirable effects can, thus,
be substantially alleviated in the context of HCC chemotherapy. Clinical studies in HCC patients
utilizing Utt-B, is a contiguous key step to promote this drug to the clinic.
