Modulatory Effects of Chalcone Thio-Derivatives on NF-κB and STAT3 Signaling Pathways in Hepatocellular Carcinoma Cells - A Study on Selected Active Compounds

Sep 21, 2026

Our previous studies showed thio-chalcone derivatives can modulate Nrf2, NF-κB, and STAT3 signaling in cancer models. This work evaluates four selected chalcone thio-derivatives for their effects on NF-κB and STAT3 pathways in human hepatocellular carcinoma cells, linked to inflammation and proliferation. Cell survival was measured in HepG2 and THLE-2 lines, while NF-κB/STAT3 activation and downstream proteins were analyzed by Western blot and qRT-PCR. Proximal kinase phosphorylation was assessed using MagneticBead-Based Multiplex Immunoassay. Derivatives 1 and 5 notably affected viability, cell cycle, apoptosis, and pathway activation with low toxicity to noncancerous cells. Findings support potential use of these synthetic thio-chalcones in molecularly targeted combination therapy for HCC.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages20

Reading Time50 min

AccessFree to download

Introduction

NF-κB in hepatocellular carcinoma progression

STAT3 activation and clinical relevance

Rationale for chalcone thio-derivatives

Article Modulatory Effects of Chalcone Thio-Derivatives on NF-κB and STAT3 Signaling Pathways in Hepatocellular Carcinoma Cells: A Study on Selected Active Compounds Katarzyna Papierska 1, *, Eliza Judasz 1, Wiktoria Toni ´nska 1, Maciej Kubicki 2 and Violetta Krajka-Ku´zniak 1 Citation: Papierska, K.; Judasz, E.; Toni ´nska, W.; Kubicki, M.; Krajka-Ku´zniak, V. Modulatory Effects of Chalcone Thio-Derivativeson NF-κB and STAT3 Signaling Pathways in Hepatocellular Carcinoma Cells: A Study on Selected Active Compounds. Int. J. Mol. Sci. 2024, 25, 10739. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/ijms251910739](10.3390/ijms251910739) Academic Editors: Susumu Ohya and Katsuhiko Muraki Received: 19 August 2024 Revised: 29 September 2024 Accepted: 3 October 2024 Published: 5 October 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Pozna ´n, Poland; [judasz.eliza@gmail.com](judasz.eliza@gmail.com) (E.J.); [wiktoria.toninska99@gmail.com](wiktoria.toninska99@gmail.com) (W.T.); [vkrajka@ump.edu.pl](vkrajka@ump.edu.pl) (V.K.-K.) 2 Faculty of Chemistry, Adam Mickiewicz University in Pozna ´n, Uniwersytetu Pozna ´nskiego 8, 61-712 Pozna ´n, Poland; [maciej.kubicki@amu.edu.pl](maciej.kubicki@amu.edu.pl) * Correspondence: [kpapierska@ump.edu.pl](kpapierska@ump.edu.pl) Abstract: Our previous studies demonstrated the modulatory effects of new synthetic thio-chalcone derivatives in dishes on the Nrf2, NF-κB, and STAT3 signaling pathways in colon cancer cells. This study aimed to evaluate the effect of four selected active chalcone thio-derivatives on the NF-κB and STAT3 signaling pathways involved in inflammatory processes and cell proliferation in human liver cancer cells. Cell survival was assessed for cancer (HepG2) and normal (THLE-2) cell lines. Activation of NF-κB and STAT3 signaling pathways and the expression of proteins controlled by these pathways were estimated by Western blot, and qRT-PCR assessed the expression of NF-κB and STAT3 target genes. We also evaluated the impact on the selected kinases responsible for the phosphorylation of the studied transcription factors by MagneticBead-Based Multiplex Immunoassay. Among the thio-derivatives tested, especially derivatives 1 and 5, there was an impact on cell viability, cell cycle, apoptosis, and activation of NF-κB and STAT3 pathways in hepatocellular carcinoma (HCC), which confirms the possibilities of using them in combinatorial molecular targeted therapy of HCC. The tested synthetic thio-chalcones exhibit anticancer activity by initiating proapoptotic processes in HCC while showing low toxicity to non-cancerous cells. These findings confirm the possibility of using chalcone thio-derivatives in molecularly targeted combination therapy for HCC. Keywords: anakoinosis; apoptosis; p53; TNF-α; STAT3; NF-κB; thio-chalcone derivatives; hepatocellular carcinoma cells 1. Introduction Liver cancer is a highly heterogeneous cancer that remains one of the most difficult oncology challenges. Inflammatory mediators, whose activators or targets are transcriptional factors such as Signal Transducer and Activator of Transcription 3 (STAT3), and Nuclear Factor kappa B (NF-κB) play a vital role in the development of carcinogenesis hepatocellular carcinoma (HCC) [1] . In normal cells, the NF-κB is a set of dimeric subunits in the cytoplasm bound to inhibitory IkB proteins. Chronic inflammation is associated with the high incidence of HCC, characterized by increased NF-κB activity and overexpression of genes encoding proteins involved i

FAQs

What is the purpose of testing the four chalcone thio-derivatives?

To evaluate their effects on NF-κB and STAT3 signaling pathways involved in inflammatory processes and cell proliferation in human liver cancer cells.

Which cell lines were used to assess cell survival and anticancer effects?

HepG2 cancer cells and THLE-2 normal cells were used to measure cell survival and related biological outcomes.

How were NF-κB and STAT3 pathway activation and target gene expression measured?

NF-κB and STAT3 activation and controlled proteins were assessed using Western blot, while qRT-PCR measured NF-κB and STAT3 target gene expression.

Sep 21, 2026

Uploaded by River Wang