Structural changes and anti-hepatocellular carcinoma activity of interferon-γ after interaction with sinensetin.

Feiling Feng, Tiehua Li, Yingchao Liang, Wei Gao, Liang Yang

Journal: International journal of biological macromolecules 2023;253(Pt 1):126392

PMID: 37595707

Full Text on Elsevier Science View on PubMed

Abstract

Exploring the interaction of small molecules with therapeutic proteins can provide useful information about development of ligand-protein complexes as synergistically therapeutic platforms. In this study, the interaction of sinensetin with human interferon gamma (IFNγ) was evaluated experimentally and theoretically. Also, the synergistic effects of IFNγ- sinensetin complex on the inhibition of hepatocellular carcinoma HepG2 cell proliferation were assessed by cell viability and quantitative real time PCR assays. It was realized that sinensetin interacts with IFNγ through a static quenching mechanism and hydrophobic forces mediated by presence of Lys55 and Lys58 amino acid residues in the binding site were the main contributing forces in the spontaneous formation of IFNγ-sinensetin complex. Also, the interaction of sinensetin with IFNγ did not induce a significant change in the secondary and tertiary structure of the protein. Cellular assays revealed a synergistic effect of sinensetin on IFNγ -triggered anticancer action in HepG2 cells through overexpression of caspase-3 mRNA and protein. In conclusion, this study may hold great promise for the development of potential ligand- protein complexes for therapeutic purposes.

Address: Department of Biliary Tract Surgery I, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China.; Department of Radiotherapy, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China.; Department of Radiation Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 201204, China.; Department of Radiation Oncology, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200434, China. Electronic address: [email protected].; Department of Radiation Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 201204, China. Electronic address: [email protected].

DOI: 10.1016/j.ijbiomac.2023.126392

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https://linkinghub.elsevier.com/retrieve/pii/S0141...

MeSH Terms: Humans, Interferon-gamma, Carcinoma, Hepatocellular, Ligands, Liver Neoplasms