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

Abstract

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.

Cardamonin Presents in Vivo Activity against Schistosoma mansoni and Inhibits Potato Apyrase

“…Moreover, we also analyzed ADMET (Absorption, Distribution, Metabolism, Elimination, Toxicity) properties to confirm whether cardamonin could be considered a promising drug candidate. In this sense, an acute toxicity study demonstrated that cardamonin is safe and well‐tolerated up to 2000 mg/kg in mice [34] . Also, the assessment results ( Table 3) showed that cardamonin does not violate any of Lipinski's rule of five [33,34] .…”

“…In this sense, an acute toxicity study demonstrated that cardamonin is safe and well‐tolerated up to 2000 mg/kg in mice [34] . Also, the assessment results ( Table 3) showed that cardamonin does not violate any of Lipinski's rule of five [33,34] . Considering the Log P values, which may be related to the molecule absorption and should be less than 5, we could suggest that cardamonin has good absorption and oral bioavailability.…”

Thymoquinone Inhibits Growth of Acute Myeloid Leukemia Cells through Reversal SHP-1 and SOCS-3 Hypermethylation: In Vitro and In Silico Evaluation

“…Pubchem was used to make sdf format and converted to PDB format using Pymol and further used for docking studies. The starting structures of the proteins were prepared using AutoDock tools [65]. Water molecules were deleted, and polar hydrogen and Kollman charges were added to the protein starting structure.…”

Anticancer Activity of Natural and Synthetic Chalcones

“…The chalcone also has Π–Π bonds with TYR204. The free binding energy of 5-fluorouracil is superior to that of CD, which is explained by the stabilization of the active pocket by two aromatic residues in the structure of the chalcone [ 212 ].…”