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bioRxiv · 10.1101/2022.02.01.478749

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

Swetha, M.·Keerthana, C. K.·Rayginia, T. P.·Nath, L. R.·Haritha, N. H.·Kalimuthu, K.·Jannet, S.·Pillai, S.·Harikumar, K. B.·Sundaram, S.·Anto, N. P.·Wu, D. H.·Lankalapalli, R. S.·Towner, R.·Isakov, N.·Sathyaseelan, D.·Anto, R. J.
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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.

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Swetha, M., Keerthana, C. K., Rayginia, T. P., Nath, L. R., Haritha, N. H., Kalimuthu, K., Jannet, S., Pillai, S., Harikumar, K. B., Sundaram, S., Anto, N. P., Wu, D. H., Lankalapalli, R. S., Towner, R., Isakov, N., Sathyaseelan, D., Anto, R. J.. 2022-02-04. Augmented efficacy of uttroside B over sorafenib in a murine model of human hepatocellular carcinoma. https://doi.org/10.1101/2022.02.01.478749

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