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
Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur 50603, Malaysia.
Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia.
Biomedicines. 2020 Dec 9;8(12):586. doi: 10.3390/biomedicines8120586.
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.
小豆蔻明（CADMN）对人肝癌细胞（HepG2）具有体外抗增殖和凋亡作用。本研究旨在探讨CADMN对无胸腺裸鼠人肝癌异种移植瘤的体内抗肿瘤作用，并研究该化合物的分子对接和安全性。急性毒性研究表明，在ICR小鼠中，高达2000 mg/kg的CADMN是安全且耐受性良好的。与未治疗的对照组相比，在异种移植裸鼠中口服50 mg/kg/天的CADMN可显著抑制肿瘤生长，且无明显毒性迹象。免疫组织化学分析显示，与未治疗的对照组相比，治疗组中增殖蛋白如PCNA和Ki-67的表达下调。此外，免疫荧光分析显示，抗凋亡蛋白Bcl-2显著下调，而与未治疗的小鼠相比，用25和50 mg/kg CADMN处理的裸鼠中促凋亡蛋白Bax显著上调。研究结果还显示NF-κB-p65和Ikkβ蛋白表达下调，表明CADMN使NF-κB通路失活。分子对接研究表明，CADMN在肝癌细胞中与各种凋亡和增殖靶点具有良好的对接性能和结合亲和力。总之，CADMN可能是一种潜在的抗肝癌候选药物。然而，其他药代动力学和药效学特性需要进一步深入研究。
