Design, Synthesis, and Antitumor Evaluation of Novel Mono-Carbonyl Curcumin Analogs in Hepatocellular Carcinoma Cell

Curcumin is a polyphenolic natural product that has promising anticancer properties. However, its clinical utility is limited by its chemical instability and poor metabolic properties. In this paper, a series of new curcumin analogs were synthesized and found to be potent antiproliferative agents ag...

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Published in:Pharmaceuticals (Basel, Switzerland) Switzerland), 2022-07, Vol.15 (8), p.950
Main Authors: Yu, Pan, Cao, Weiya, Zhao, Linguo, Han, Qing, Yang, Shilong, Yang, Kepeng, Pan, Xiaolei, Wang, Qianyun, Wang, Yuan
Format: Article
Language:English
Subjects:
AKT inhibition
Antimitotic agents
Antineoplastic agents
antitumor activity
Apoptosis
Bioavailability
Biological activity
Carbon
Carbonyl compounds
Care and treatment
Cell adhesion & migration
cell apoptosis
Cell growth
Chemical properties
Cloning
curcumin analogs
Gene expression
Health aspects
Hepatoma
Hydrocarbons
Liver cancer
molecular dynamics simulations
Pharmaceutical research
Production processes
Protein expression
Proteins
Turmeric
Wound healing
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Summary:Curcumin is a polyphenolic natural product that has promising anticancer properties. However, its clinical utility is limited by its chemical instability and poor metabolic properties. In this paper, a series of new curcumin analogs were synthesized and found to be potent antiproliferative agents against the HepG2 cell line by MTT assay. In general, Group B with single ketone and group C with chalcone were markedly more cytotoxic than group A with diketone. Compound B5 was found as the most potent analog (IC50 = 11.33 μM) compared to curcumin (IC50 = 32.83 μM) and the mechanism of its cytotoxicity was investigated. The result of the wound healing assay indicated B5 strong potential to suppress HepG2 cell migration in a dose- and time-dependent manner. Subsequent assays (including JC-1 staining, Bcl-2, and caspase 3 protein levels by Western blotting) confirmed that B5 exposure induced apoptosis in HepG2 cells. Curcumin-induced comprehensive transcriptomes profile, Western blotting, molecular docking, and molecular dynamics analysis showed that the mechanism may relate to the regulation of cellular metabolic process and the expression of AKT protein. Taken together, we could conclude that curcumin and its analogs induced HepG2 cell proliferation, migration, and apoptosis via AKT signaling pathway and the mitochondrial death pathway. This study could lay the foundation for optimizing curcumin and provide valuable information for finding novel anti-HCC drugs.
ISSN:1424-8247
1424-8247
DOI:10.3390/ph15080950