Augmented Efficacy of Uttroside B over Sorafenib in a Murine Model of Human Hepatocellular Carcinoma.
Mundanattu SwethaChenicheri K KeerthanaTennyson P RayginiaLekshmi R NathNair Hariprasad HarithaAnwar ShabnaKalishwaralal KalimuthuArun K ThangarasuSreekumar U AiswaryaSomaraj JannetSreekumar PillaiKuzhuvelil B HarikumarSankar SundaramNikhil Ponnoor AntoDee H WuRavi S LankalapalliRheal TownerNoah IsakovSathyaseelan S DeepaRuby John AntoPublished in: Pharmaceuticals (Basel, Switzerland) (2022)
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.
Keyphrases
- drug induced
- liver injury
- endothelial cells
- liver failure
- end stage renal disease
- oxidative stress
- adverse drug
- newly diagnosed
- chronic kidney disease
- metabolic syndrome
- machine learning
- early onset
- emergency department
- ejection fraction
- insulin resistance
- type diabetes
- induced pluripotent stem cells
- intensive care unit
- hepatitis b virus
- electronic health record
- skeletal muscle
- aortic dissection
- wild type