Inhibitory effect of protonic bis(5-amino-1,10-phenanthroline) on proliferation of hepatocellular carcinoma and its molecular mechanism

The incidence of HCC continues to increase rapidly in recent years. the principle of developing anti-HCC drugs is to specifically kill tumor cells, without affecting the function of normal cells. Here we synthesized a novel protonic compound bis(5-amino-1,10-phenanthroline) (P-BAP), and the antitumo...

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Bibliographic Details
Main Authors: Zizhen Zhao, Chen Fu, Yuping Zhang, Yingying Zhang, Xiaoxi Yang, Ailing Fu
Format: Article
Language:English
Published: Elsevier 2022-08-01
Series:Arabian Journal of Chemistry
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Online Access:http://www.sciencedirect.com/science/article/pii/S1878535222002982
Description
Summary:The incidence of HCC continues to increase rapidly in recent years. the principle of developing anti-HCC drugs is to specifically kill tumor cells, without affecting the function of normal cells. Here we synthesized a novel protonic compound bis(5-amino-1,10-phenanthroline) (P-BAP), and the antitumor activity was explored in vitro and in vivo. The results showed that P-BAP could selectively inhibit the proliferation of tumor cells, and induce HCC apoptosis. In HCC-bearing mice, P-BAP could effectively retard the tumor growth, even completely eliminate the tumors at the dose of 5 mg/kg, and meanwhile P-BAP had no significant effect on mouse body weight. Mechanism analysis revealed that P-BAP could down-regulate the protein expressions of pleomorphic adenoma gene like-2 (PLAGL2), HIF-1α and β-catenin, and up-regulate the levels of pro-apoptotic protein BAX and BNIP3. In addition, P-BAP could reduce mitochondrial respiratory chain complex activities, leading to insufficient ATP production. The study provides a new approach for designing selective antitumor drugs, and suggests that P-BAP would be a potential candidate for HCC therapy.
ISSN:1878-5352