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Cardamonin Exerts Antitumor Effect on Human Hepatocellular Carcinoma Xenografts in Athymic Nude Mice through Inhibiting NF-κβ Pathway

Cardamonin (CADMN) exerts an in vitro antiproliferative and apoptotic actions against human hepatocellular carcinoma cells (HepG2). This study aimed to investigate the in vivo anti-tumorigenic action of CADMN against human hepatocellular carcinoma xenografts in an athymic nude mice, as well as to st...

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Autores principales: Badroon, Nassrin, Abdul Majid, Nazia, Al-Suede, Fouad Saleih R., Nazari V., Mansoureh, Giribabu, Nelli, Abdul Majid, Amin Malik Shah, Eid, Eltayeb E. M., Alshawsh, Mohammed Abdullah
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764268/
https://www.ncbi.nlm.nih.gov/pubmed/33316979
http://dx.doi.org/10.3390/biomedicines8120586
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author Badroon, Nassrin
Abdul Majid, Nazia
Al-Suede, Fouad Saleih R.
Nazari V., Mansoureh
Giribabu, Nelli
Abdul Majid, Amin Malik Shah
Eid, Eltayeb E. M.
Alshawsh, Mohammed Abdullah
author_facet Badroon, Nassrin
Abdul Majid, Nazia
Al-Suede, Fouad Saleih R.
Nazari V., Mansoureh
Giribabu, Nelli
Abdul Majid, Amin Malik Shah
Eid, Eltayeb E. M.
Alshawsh, Mohammed Abdullah
author_sort Badroon, Nassrin
collection PubMed
description Cardamonin (CADMN) exerts an in vitro antiproliferative and apoptotic actions against human hepatocellular carcinoma cells (HepG2). This study aimed to investigate the in vivo anti-tumorigenic action of CADMN against human hepatocellular carcinoma xenografts in an athymic nude mice, as well as to study the molecular docking and safety profile of this compound. Acute toxicity study demonstrated that CADMN is safe and well-tolerated up to 2000 mg/kg in ICR mice. Oral administration of 50 mg/kg/day of CADMN in xenografted nude mice showed a significant suppression in tumor growth as compared to untreated control group without pronounced toxic signs. Immunohistochemistry assay showed downregulation of proliferative proteins such as PCNA and Ki-67 in treated groups as compared to untreated control. Additionally, immunofluorescence analysis showed a significant downregulation in anti-apoptotic Bcl-2 protein, whereas pre-apoptotic Bax protein was significantly upregulated in nude mice treated with 25 and 50 mg/kg CADMN as compared to untreated mice. The findings also exhibited down-regulation of NF-κB-p65, and Ikkβ proteins, indicating that CADMN deactivated NF-κB pathway. The molecular docking studies demonstrated that CADMN exhibits good docking performance and binding affinities with various apoptosis and proliferation targets in hepatocellular cancer cells. In conclusion, CADMN could be a potential anticancer candidate against hepatocellular carcinoma. Other pharmacokinetics and pharmacodynamics properties, however, need to be further investigated in depth.
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spelling pubmed-77642682020-12-27 Cardamonin Exerts Antitumor Effect on Human Hepatocellular Carcinoma Xenografts in Athymic Nude Mice through Inhibiting NF-κβ Pathway Badroon, Nassrin Abdul Majid, Nazia Al-Suede, Fouad Saleih R. Nazari V., Mansoureh Giribabu, Nelli Abdul Majid, Amin Malik Shah Eid, Eltayeb E. M. Alshawsh, Mohammed Abdullah Biomedicines Article Cardamonin (CADMN) exerts an in vitro antiproliferative and apoptotic actions against human hepatocellular carcinoma cells (HepG2). This study aimed to investigate the in vivo anti-tumorigenic action of CADMN against human hepatocellular carcinoma xenografts in an athymic nude mice, as well as to study the molecular docking and safety profile of this compound. Acute toxicity study demonstrated that CADMN is safe and well-tolerated up to 2000 mg/kg in ICR mice. Oral administration of 50 mg/kg/day of CADMN in xenografted nude mice showed a significant suppression in tumor growth as compared to untreated control group without pronounced toxic signs. Immunohistochemistry assay showed downregulation of proliferative proteins such as PCNA and Ki-67 in treated groups as compared to untreated control. Additionally, immunofluorescence analysis showed a significant downregulation in anti-apoptotic Bcl-2 protein, whereas pre-apoptotic Bax protein was significantly upregulated in nude mice treated with 25 and 50 mg/kg CADMN as compared to untreated mice. The findings also exhibited down-regulation of NF-κB-p65, and Ikkβ proteins, indicating that CADMN deactivated NF-κB pathway. The molecular docking studies demonstrated that CADMN exhibits good docking performance and binding affinities with various apoptosis and proliferation targets in hepatocellular cancer cells. In conclusion, CADMN could be a potential anticancer candidate against hepatocellular carcinoma. Other pharmacokinetics and pharmacodynamics properties, however, need to be further investigated in depth. MDPI 2020-12-09 /pmc/articles/PMC7764268/ /pubmed/33316979 http://dx.doi.org/10.3390/biomedicines8120586 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Badroon, Nassrin
Abdul Majid, Nazia
Al-Suede, Fouad Saleih R.
Nazari V., Mansoureh
Giribabu, Nelli
Abdul Majid, Amin Malik Shah
Eid, Eltayeb E. M.
Alshawsh, Mohammed Abdullah
Cardamonin Exerts Antitumor Effect on Human Hepatocellular Carcinoma Xenografts in Athymic Nude Mice through Inhibiting NF-κβ Pathway
title Cardamonin Exerts Antitumor Effect on Human Hepatocellular Carcinoma Xenografts in Athymic Nude Mice through Inhibiting NF-κβ Pathway
title_full Cardamonin Exerts Antitumor Effect on Human Hepatocellular Carcinoma Xenografts in Athymic Nude Mice through Inhibiting NF-κβ Pathway
title_fullStr Cardamonin Exerts Antitumor Effect on Human Hepatocellular Carcinoma Xenografts in Athymic Nude Mice through Inhibiting NF-κβ Pathway
title_full_unstemmed Cardamonin Exerts Antitumor Effect on Human Hepatocellular Carcinoma Xenografts in Athymic Nude Mice through Inhibiting NF-κβ Pathway
title_short Cardamonin Exerts Antitumor Effect on Human Hepatocellular Carcinoma Xenografts in Athymic Nude Mice through Inhibiting NF-κβ Pathway
title_sort cardamonin exerts antitumor effect on human hepatocellular carcinoma xenografts in athymic nude mice through inhibiting nf-κβ pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764268/
https://www.ncbi.nlm.nih.gov/pubmed/33316979
http://dx.doi.org/10.3390/biomedicines8120586
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