Evaluation of uttroside B, a saponin from Solanum nigrum Linn, as a promising chemotherapeutic agent against hepatocellular carcinoma
Authors: Lekshmi R Nath
Shabna Shah
Jaggaiah N Gorantla
Ravi S Lankalapalli
Arun Kumar T Thulasidasan
Shabna Anwer
Sankar Sundaram
Sophia M Joseph
Udaya K Marelli
Vinod Vijayakurup
Jayesh Antony
Kollery Suresh Veena
Ruby John Anto
Journal: Scientific Reports (2016)
Discipline: Multidisciplinary
Keywords: uttroside B; liver cancer; Solanum nigrum Linn; cytotoxicity; HepG2
Affiliations: Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram-695014, Kerala, India., Chemical Sciences and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram-695019, Kerala, India., Department of Pathology, Government Medical College, Thiruvananthapuram-695011, Kerala, India., Division of Organic Chemistry, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune-411008, India.

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

Retracted: No

PubPeer comments:
 Figure 3D appears to include a repeated image. ***  , 
 #1 Dear Editor, Thank you for your comment. The figure in question (fig 3D) shows images of morphological changes induced by uttroside B in HepG2 cells. For both images representing the cells treated with 100nM and 300nM uttroside B, we have given the same image of cells treated with 300nM of the compound, by mistake. Uttroside B starts causing significant morphological changes from 250 nM onwards and the IC50 of the compound is 500nM. Hence the figure no way affects the conclusions of the experiment. We sincerely regret the error and apologize to all readers for the concern it caused. We will soon apply for a corrigendum incorporating the correction. Thank you for reading our paper and for the feedback. Sincerely, Ruby John Anto , 
 November 18, 2020 u201cCorrection to: Scientific Reports https: doi.org 10.1038 srep36318, published online 03 November 2016 This Article contains errors. In Figure 2A, the NMR spectrum of uttroside A is provided instead of uttroside B. The correct Figure 2A appears below as Figure 1. Consequently, in the Results section, u201cThe key information pertaining to steroidal furanose ring include H-21 methyl group at u03b4H 0.99 ppm (3H, d, Ju2009=u20097 Hz), and hemiketal carbon C-22 at u03b4C 112.5 ppm. Owing to complex pattern of signals arising due to sugars in the region between 3 to 4 ppm, the isolated saponin was peracetylated (Fig. 2A).u201d should read: u201cThe key information pertaining to steroidal furanose ring include H-21 methyl group at u03b4H 1.00 ppm (3H, d, Ju2009=u20097 Hz), and hemiketal carbon C-22 at u03b4C 110.5 ppm. Owing to complex pattern of signals arising due to sugars in the region between 3 to 4 ppm (Fig. 2A), the isolated saponin was peracetylated.u201d u201cMS-MS analysis in negative mode afforded ions at m z 1081.5 (M-xyl-H), 919.5 (M-hex-H), 757.4 (M-hex-hex-H), and in positive mode afforded ions at m z 1235.5 (M-H2O + K), 1197.5 (M- H2O), 1073.4 (M- H2O-hexose + K), 741.4 (M- H2O-hex-hex-xyl+H), 579.3 (M- H2O-hex-hex-xyl-hex+H), 417.3 (M- H2O-hex-hex-xyl-hex-hex+H), 163.06 (M-hex-hex-xyl-hex-hex-furostanol + H), which further confirmed that the isolated saponin is uttroside B with a molecular weight of 1215.34 Da (Supplementary Figures S2, S3 and S4).u201d should read: u201cMS-MS analysis in negative mode afforded ions at m z 1081.5 (M-xyl-H), 919.5 (M-xyl-hex-H), 757.4 (M-xyl-hex-hex-H), and in positive mode afforded ions at m z 1235.5 (M- H2O + K), 1197.5 (M- H2O +H), 1073.4 (M- H2O-hex + K), 741.4 (M- H2O-hex-hex-xyl+H), 579.3 (M- H2O-hex-hex-xyl-hex+H), 417.3 (M- H2O-hex-hex-xyl-hex-hex+H), 163.06 (M-hex-hex-xyl-hex-furostanol), which further confirmed that the isolated saponin is uttroside B with a molecular weight of 1215.34 Da (Supplementary Figures S2, S3 and S4).u201d Finally, in Figure 3D, the 100 nM image is a duplication of the 300 nM image. The correct Figure 3D appears below as Figure 2.u201d *** The correct version of Figure 2A.  *** The correct version of Figure 3D.  ,