Evaluation of uttroside B, a saponin from Solanum nigrum Linn, as a promising chemotherapeutic agent against hepatocellular carcinoma.
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.
Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram-695014, Kerala, India.
Lekshmi R
LR
Nath
Chemical Sciences and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram-695019, Kerala, India.
Jaggaiah N
JN
Gorantla
Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram-695014, Kerala, India.
Arun Kumar T
AK
Thulasidasan
Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram-695014, Kerala, India.
Vinod
V
Vijayakurup
Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram-695014, Kerala, India.
Shabna
S
Shah
Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram-695014, Kerala, India.
Shabna
S
Anwer
Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram-695014, Kerala, India.
Sophia M
SM
Joseph
Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram-695014, Kerala, India.
Jayesh
J
Antony
Chemical Sciences and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram-695019, Kerala, India.
Kollery Suresh
KS
Veena
Department of Pathology, Government Medical College, Thiruvananthapuram-695011, Kerala, India.
Sankar
S
Sundaram
Division of Organic Chemistry, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune-411008, India.
Udaya K
UK
Marelli
Chemical Sciences and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram-695019, Kerala, India.
Ravi S
RS
Lankalapalli
Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram-695014, Kerala, India.
Ruby John
RJ
Anto
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D012503:Saponins / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D032324:Solanum nigrum / Q000737:chemistry*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; D012503:Saponins; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases