Augmented Efficacy of Uttroside B over Sorafenib in a Murine Model of Human Hepatocellular Carcinoma
We previously reported the remarkable potency of uttroside B (Utt-B), saponin-isolated and characterized in our lab from <i>Solanum nigrum</i> 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 effic...
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MDPI AG
2022-05-01
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| Online Access: | https://www.mdpi.com/1424-8247/15/5/636 |
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| author | Mundanattu Swetha Chenicheri K. Keerthana Tennyson P. Rayginia Lekshmi R. Nath Nair Hariprasad Haritha Anwar Shabna Kalishwaralal Kalimuthu Arun K. Thangarasu Sreekumar U. Aiswarya Somaraj Jannet Sreekumar Pillai Kuzhuvelil B. Harikumar Sankar Sundaram Nikhil Ponnoor Anto Dee H. Wu Ravi S. Lankalapalli Rheal Towner Noah Isakov Sathyaseelan S. Deepa Ruby John Anto |
| author_facet | Mundanattu Swetha Chenicheri K. Keerthana Tennyson P. Rayginia Lekshmi R. Nath Nair Hariprasad Haritha Anwar Shabna Kalishwaralal Kalimuthu Arun K. Thangarasu Sreekumar U. Aiswarya Somaraj Jannet Sreekumar Pillai Kuzhuvelil B. Harikumar Sankar Sundaram Nikhil Ponnoor Anto Dee H. Wu Ravi S. Lankalapalli Rheal Towner Noah Isakov Sathyaseelan S. Deepa Ruby John Anto |
| author_sort | Mundanattu Swetha |
| collection | DOAJ |
| description | We previously reported the remarkable potency of uttroside B (Utt-B), saponin-isolated and characterized in our lab from <i>Solanum nigrum</i> 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. |
| first_indexed | 2024-03-10T03:09:46Z |
| format | Article |
| id | doaj.art-b186c71c587e4df097a4a4b437a83fd0 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T03:09:46Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-b186c71c587e4df097a4a4b437a83fd02023-11-23T12:35:49ZengMDPI AGPharmaceuticals1424-82472022-05-0115563610.3390/ph15050636Augmented Efficacy of Uttroside B over Sorafenib in a Murine Model of Human Hepatocellular CarcinomaMundanattu Swetha0Chenicheri K. Keerthana1Tennyson P. Rayginia2Lekshmi R. Nath3Nair Hariprasad Haritha4Anwar Shabna5Kalishwaralal Kalimuthu6Arun K. Thangarasu7Sreekumar U. Aiswarya8Somaraj Jannet9Sreekumar Pillai10Kuzhuvelil B. Harikumar11Sankar Sundaram12Nikhil Ponnoor Anto13Dee H. Wu14Ravi S. Lankalapalli15Rheal Towner16Noah Isakov17Sathyaseelan S. Deepa18Ruby John Anto19Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695014, Kerala, IndiaDivision of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695014, Kerala, IndiaDivision of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695014, Kerala, IndiaDivision of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695014, Kerala, IndiaDivision of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695014, Kerala, IndiaDivision of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695014, Kerala, IndiaDivision of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695014, Kerala, IndiaChemical Sciences and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram 695019, Kerala, IndiaDivision of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695014, Kerala, IndiaDivision of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695014, Kerala, IndiaDepartment of Surgical Oncology, Jubilee Mission Medical College and Research Institute, Thrissur 680005, Kerala, IndiaDivision of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695014, Kerala, IndiaDepartment of Pathology, Government Medical College, Kottayam 686008, Kerala, IndiaThe Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O. Box 653, Beer Sheva 84105, IsraelSection of Medical Physics, Department of Radiological Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USAChemical Sciences and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram 695019, Kerala, IndiaDepartments of Pathology and Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USAThe Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O. Box 653, Beer Sheva 84105, IsraelDepartment of Biochemistry and Molecular Biology, and Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADivision of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695014, Kerala, IndiaWe previously reported the remarkable potency of uttroside B (Utt-B), saponin-isolated and characterized in our lab from <i>Solanum nigrum</i> 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.https://www.mdpi.com/1424-8247/15/5/636uttroside Bsorafenibhepatocellular carcinomachemotherapeuticapoptosis |
| spellingShingle | Mundanattu Swetha Chenicheri K. Keerthana Tennyson P. Rayginia Lekshmi R. Nath Nair Hariprasad Haritha Anwar Shabna Kalishwaralal Kalimuthu Arun K. Thangarasu Sreekumar U. Aiswarya Somaraj Jannet Sreekumar Pillai Kuzhuvelil B. Harikumar Sankar Sundaram Nikhil Ponnoor Anto Dee H. Wu Ravi S. Lankalapalli Rheal Towner Noah Isakov Sathyaseelan S. Deepa Ruby John Anto Augmented Efficacy of Uttroside B over Sorafenib in a Murine Model of Human Hepatocellular Carcinoma Pharmaceuticals uttroside B sorafenib hepatocellular carcinoma chemotherapeutic apoptosis |
| title | Augmented Efficacy of Uttroside B over Sorafenib in a Murine Model of Human Hepatocellular Carcinoma |
| title_full | Augmented Efficacy of Uttroside B over Sorafenib in a Murine Model of Human Hepatocellular Carcinoma |
| title_fullStr | Augmented Efficacy of Uttroside B over Sorafenib in a Murine Model of Human Hepatocellular Carcinoma |
| title_full_unstemmed | Augmented Efficacy of Uttroside B over Sorafenib in a Murine Model of Human Hepatocellular Carcinoma |
| title_short | Augmented Efficacy of Uttroside B over Sorafenib in a Murine Model of Human Hepatocellular Carcinoma |
| title_sort | augmented efficacy of uttroside b over sorafenib in a murine model of human hepatocellular carcinoma |
| topic | uttroside B sorafenib hepatocellular carcinoma chemotherapeutic apoptosis |
| url | https://www.mdpi.com/1424-8247/15/5/636 |
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