Evaluation of uttroside B, a saponin from Solanum nigrum Linn, as a promising chemotherapeutic agent against hepatocellular carcinoma

Abstract

We report, for the first time, the remarkable efficacy of uttroside B, a potent saponin from Solanum nigrum Linn, against liver cancer. The compound has been isolated and characterized from the leaves of Solanum nigrum Linn, a plant widely used in traditional medicine and is a rich resource of several anticancer molecules. Uttroside B, that comprises of β-D-glucopyranosyl unit at C-26 of the furostanol and β-lycotetraosyl unit at C-3, is ten times more cytotoxic to the liver cancer cell line, HepG2 (IC50: 0.5 μM) than sorafenib (IC50: 5.8 μM), the only FDA-approved drug for liver cancer. Moreover, it induces cytotoxicity in all liver cancer cell lines, irrespective of their HBV status, while being non-toxic to normal immortalized hepatocytes. It induces apoptosis in HepG2 cells by down-regulating mainly the activation of MAPK and mTOR pathways. The drastic reduction in HepG2-xenograft tumor size achieved by uttroside B in NOD-SCID mice and substantiation of its biological safety through both acute and chronic toxicity studies in Swiss albino mice warrants clinical validation of the molecule against hepatic cancer, for which, the chemotherapeutic armamentarium currently has limited weapons.

Separation and evaluation of natural antileishmanial potential against Leishmania major and infuntum isolated from the Tunisia strains

“…As described in the introduction section, recently saponins have become a research hotspot due to their multiple and strong bioactivities, especially their cytotoxic activities on a series of tumor cell lines related to their chemical structure (Bouabdallah et al, 2015;Nath et al, 2016;Zhang et al, 2016;Zhou et al, 2017). However our result also confirmed that the n-butanolic extract (saponin fraction) exhibited the best inhibitory activity on both of the leishmania parasites tested (Table II).…”

Emerging themes of regulation of oncogenic proteins by Solanum nigrum and its bioactive molecules in different cancers

“…Activation of c-Jun N-terminal kinase was significantly inhibited in cancer cells after treatment with uttroside B. 6 The mTOR activation was also considerably repressed in HepG2 cells when treated with uttroside B. The 10 and 50 mg/kg doses of uttroside B were given to the experimental mice and, interestingly, tested mice did not show changes in serum aspartate aminotransferase, alkaline phosphatase, and alanine transferase.…”

“…The concentration of uttroside B, time-dependently triggered procaspase-9 cleavage into its processed fragments (p35/37 and p17). 6 Water and polyphenolic extracts of S. nigrum were significantly effective against HepG2 cells. c-Jun N-terminal kinase belongs to the family of MAPK and regulates myriad of biological processes.…”

“…6 Uttroside B comprised of β-lycotetraosyl unit at C-3 and β-D-glucopyranosyl unit at C-26 of the furostanol, which made it more effective than sorafenib. 6 Uttroside B comprised of β-lycotetraosyl unit at C-3 and β-D-glucopyranosyl unit at C-26 of the furostanol, which made it more effective than sorafenib.…”

“…6 Uttroside B comprised of β-lycotetraosyl unit at C-3 and β-D-glucopyranosyl unit at C-26 of the furostanol, which made it more effective than sorafenib. 6 There was no significant deviation from any of these parameters from their normal range, which indicated that uttroside B was pharmacologically efficient, nontoxic, and safe. Similarly, procaspase-8 cleavage into functional segments (p43/41) and procaspase-7 into its active segment (p-20) were also enhanced in cancer cells after treatment with uttroside B. Uttroside B inhibited MAPK and mammalian target of rapamycin (mTOR) signal transduction cascades.…”