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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 ?-D-glucopyranosyl unit at C-26 of the furostanol and ?-lycotetraosyl unit at C-3, is ten times more cytotoxic to the liver cancer cell line, HepG2 (IC50: 0.5??M) than sorafenib (IC50: 5.8??M), 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.

SUBMITTER: Nath LR

PROVIDER: S-EPMC5093766 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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

Nath Lekshmi R LR Gorantla Jaggaiah N JN Thulasidasan Arun Kumar T AK Vijayakurup Vinod V Shah Shabna S Anwer Shabna S Joseph Sophia M SM Antony Jayesh J Veena Kollery Suresh KS Sundaram Sankar S Marelli Udaya K UK Lankalapalli Ravi S RS Anto Ruby John RJ

Scientific reports 20161103

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, He ...[more]

PMID: 27808117

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Project description:Hepatocellular carcinoma (HCC) is a fatal and dominant form of liver cancer that currently has no effective treatment or positive prognosis. In this study, we explored the antitumor effects of cryptotanshinone (CPT) against HCC and the molecular mechanisms underlying these effects using a systems pharmacology and experimental validation approach. First, we identified a total of 296 CPT targets, 239 of which were also HCC-related targets. We elucidated the mechanisms by which CPT affects HCC through multiple network analysis, including CPT-target network analysis, protein-protein interaction network analysis, target-function network analysis, and pathway enrichment analysis. In addition, we found that CPT induced apoptosis in Huh7 and MHCC97-H ells due to increased levels of cleaved PARP, Bax, and cleaved caspase-3 and decreased Bcl-2 expression. CPT also induced autophagy in HCC cells by increasing LC3-II conversion and the expression of Beclin1 and ATG5, while decreasing the expression of p62/SQSTM1. Autophagy inhibitors (3-methyladenine and chloroquine) enhanced CPT-induced proliferation and apoptosis, suggesting that CPT-induced autophagy may protect HCC cells against cell death. Furthermore, CPT was found to inhibit the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. Interestingly, activation of PI3K by insulin-like growth factor-I inhibited CPT-induced apoptosis and autophagy, suggesting that the PI3K/AKT/mTOR signaling pathway is involved in both CPT-induced apoptosis and autophagy. Finally, CPT was found to inhibit the growth of Huh7 xenograft tumors. In conclusion, we first demonstrated the antitumor effects of CPT in Huh7 and MHCC97-H cells, both in vitro and in vivo. We elucidated the potential antitumor mechanism of CPT, which involved inducing apoptosis and autophagy by inhibiting the PI3K/Akt/mTOR signaling pathway. Our findings may provide valuable insights into the clinical application of CPT, serving as a potential candidate therapeutic agent for HCC treatment.

Project description:BACKGROUND:Traditionally, a number of medicinal plants are used to treat various types of hepatic disorders but few of them were pharmacologically evaluated for their safety and efficacy. The combination of Andrographis paniculata (Kalmegha), Tinospora cordifolia (Guduchi), and Solanum nigrum (Kakmachi) was traditionally used in Indian System of Medicine (Ayurveda) for the treatment of various liver-related disorders. OBJECTIVE:In the present study, an attempt was made to substantiate the ethnopharmacological use of a traditional formulation in hepatoprotection against paracetamol-induced hepatotoxicity. SUBJECTS AND METHODS:Swiss albino mice (weight 20-25 g) were used for this study. Intraperitoneal injection of paracetamol (500 mg/kg body weight) was used to induce hepatotoxicity. Serum levels of alanine transaminase, aspartate aminotransferase, bilirubin, alkaline phosphatase, were used as indices of liver injury. In addition total cholesterol, triglyceride, low-density lipoprotein, high-density lipoprotein and creatinine were also assayed using the standard procedure. RESULTS:Among the two different doses, pretreatment with Polyherbal extract at 500 mg/kg body weight exhibited a significant (P < 0.05) hepatoprotective activity as compared to paracetamol group. CONCLUSION:The polyherbal extract exhibits a significant hepatoprotective effect in vivo. The study contributes to its use in traditional Ayurveda system for the management of liver diseases. SUMMARY:Traditionally, a number of medicinal plants are used to treat various types of liver disorders but few of them were pharmacologically evaluated for their safety and efficacy. Combination of Andrographis paniculata (Kalmegha), Tinospora cordifolia (Guduchi), and Solanum nigrum (Kakmachi) was traditionally used in Ayurveda for the treatment of various liver related disorders. In the present study an attempt was made to validate the ethnopharmacological use of a traditional formulation in hepatoprotection against paracetamol induced hepatotoxicity. Swiss albino mice (weight 20-25 g) were used for this study. Intraperitoneal injection (IP) of paracetamol (500 mg/kg body weight) was used to induce hepatotoxicity. Serum levels of Alanine transaminase (ALT), Aspartate Aminotransferase (AST), Bilirubin, Alkaline phosphatase (ALP),. were used as indices of liver injury. In addition total cholesterol, triglyceride, Low density lipoprotein (LDL), High density lipoprotein (HDL) and creatinine were also assayed using standard procedure. Among the two different doses, pre-treatment with Polyherbal extract at 500 mg/kg body weight exhibited a significant (P < 0.05) hepatoprotective activity as compared to paracetamol group. The polyherbal extract exhibits significant hepatoprotective effect in vivo. The study contributes to its use in traditional Ayurveda system for the management of liver diseases.

Dataset Information

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

Publications

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

Similar Datasets

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