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

Badroon, Nassrin and Abdul Majid, Nazia and Al-Suede, Fouad and Nazari V., Mansoureh and Giribabu, Nelli and Abdul Majid, Amin and Eid, Eltayeb and Alshawsh, Mohammed Abdullah (2020) Cardamonin Exerts Antitumor Effect on Human Hepatocellular Carcinoma Xenografts in Athymic Nude Mice through Inhibiting NF-κβ Pathway. Biomedicines, 8 (12). p. 586. ISSN 2227-9059, DOI

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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. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Item Type: Article
Funders: FRGS grant (FP103-2019A) from the Ministry of Higher Education, Malaysia (Ref: FRGS/1/2019/SKK10/UM/02/3)
Uncontrolled Keywords: Anti-tumorigenesis; cardamonin; Hepatocellular carcinoma; Molecular docking; NF-κB pathway
Subjects: Q Science > QH Natural history > QH301 Biology
R Medicine
Divisions: Faculty of Medicine
Faculty of Science > Institute of Biological Sciences
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 04 Oct 2021 06:35
Last Modified: 04 Oct 2021 06:35

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