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ORIGINAL RESEARCH article

Front. Cell Dev. Biol.
Sec. Cancer Cell Biology
Volume 12 - 2024 | doi: 10.3389/fcell.2024.1476007
This article is part of the Research Topic Current Trends in Muscle Diseases and Their Treatment Strategies View all 5 articles

Efficacy of Natural NF-κB Inhibitors in the Treatment of Fibrosarcoma: An In Vitro Model Study

Provisionally accepted
Justyna Radzka Justyna Radzka 1Agnieszka Gizak Agnieszka Gizak 1Małgorzata Drąg-Zalesińska Małgorzata Drąg-Zalesińska 2Katarzyna Haczkiewicz Katarzyna Haczkiewicz 3Michał Kulus Michał Kulus 3Wojciech Szlasa Wojciech Szlasa 4Marzenna Podhorska-Okołów Marzenna Podhorska-Okołów 3Julita Kulbacka Julita Kulbacka 4,5*
  • 1 Department of Molecular Physiology and Neurobiology, Faculty of Biology, University of Wroclaw, Wroclaw, Poland
  • 2 Department of Human Morphology and Embryology, Wroclaw Medical University, Wroclaw, Poland
  • 3 Division of Ultrastructure Research, Department of Human Morphology and Embryology, Wroclaw Medical University, Wrocław, Poland
  • 4 Department of Molecular and Cellular Biology, Wroclaw Medical University, Wroclaw, Poland
  • 5 Department of Immunology and Bioelectrochemistry, State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania

The final, formatted version of the article will be published soon.

    NF-κB plays a pivotal role in the progression of cancers, including myosarcomas such as fibrosarcoma. The present study assessed, among others, the cytotoxicity, migration capacity and DNA damage induced by several natural compounds (berberine, curcumin, biochanin A, cucurbitacin E (CurE) and phenethyl caffeic acid (CAPE)) in cancer cells (WEHI-164) and normal muscle cells (L6). The IC50 parameters was determined for all substances following a 24-hour incubation period. The results demonstrated that the examined compounds exhibited a markedly enhanced cytotoxic effect on cancer cells relative to normal cells. Moreover, molecular docking studies indicated that CAPE, biochanin A, and CurE inhibited actin polymerisation, thereby suggesting their potential role in disrupting the cytoskeleton of cancer cells. Immunocytochemical analysis demonstrated elevated expression of caspase-3 and PARP-1 in WEHI-164 cells following treatment, thereby pointing to the induction of apoptosis. Transmission electron microscopy confirmed the presence of cellular stress and vacuolisation in cells treated with these compounds, with more pronounced effects observed in cancer cells compared to normal cells. The results indicate that natural NF-κB inhibitors may be capable of selectively targeting cancer cells, reducing their viability and inducing apoptosis, while sparing normal cells. This selectivity is of great importance for the development of safer anticancer therapies. The results of this research support the hypothesis that these natural compounds may be effective anticancer agents, particularly in the treatment of fibrosarcoma. Further in vivo studies and clinical trials are required to gain a full understanding of their mechanisms of action and potential synergies with existing chemotherapeutic agents.

    Keywords: muscle cancer, Berberine, cucurbitacin E (CurE), Curcumin, Biochanin A, caffeic acid phenethyl ester (CAPE)

    Received: 04 Aug 2024; Accepted: 06 Dec 2024.

    Copyright: © 2024 Radzka, Gizak, Drąg-Zalesińska, Haczkiewicz, Kulus, Szlasa, Podhorska-Okołów and Kulbacka. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Julita Kulbacka, Department of Molecular and Cellular Biology, Wroclaw Medical University, Wroclaw, Poland

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.