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Molecular mechanisms of the anticancer action of fustin isolated from Cotinus coggygria Scop. in MDA-MB-231 triple-negative breast cancer cell line

  • Georgi G. Antov , Zlatina I. Gospodinova EMAIL logo , Miroslav Novakovic , Vele Tesevic , Natalia A. Krasteva , Danail V. Pavlov and Stefka V. Valcheva-Kuzmanova
Published/Copyright: September 30, 2024
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Abstract

The aim of the present work was to investigate some of the molecular mechanisms and targets of the anticancer action of the bioflavonoid fustin isolated from the heartwood of Cotinus coggygria Scop. in the triple-negative breast cancer cell line MDA-MB-231. For this purpose, we applied fluorescence microscopy analysis to evaluate apoptosis, necrosis, and mitochondrial integrity, wound healing assay to study fustin antimigratory potential and quantitative reverse transcription-polymerase chain reaction to analyze the expression of genes associated with cell cycle control, programmed cell death, metastasis, and epigenetic alterations. A complex network-based bioinformatic analysis was also employed for protein–protein network construction, hub genes identification, and functional enrichment. The results revealed a significant induction of early and late apoptotic and necrotic events, a slight alteration of the mitochondria-related fluorescence, and marked antimotility effect after fustin treatment. Of 34 analyzed genes, seven fustin targets were identified, of which CDKN1A, ATM, and MYC were significantly enriched in pathways such as cell cycle, intrinsic apoptotic signaling pathway in response to DNA damage and generic transcription pathway. Our findings outline some molecular mechanisms of the anticancer action of fustin pointing it out as a potential oncotherapeutic agent and provide directions for future in vivo research.


Corresponding author: Zlatina I. Gospodinova, Laboratory of Genome Dynamics and Stability, Institute of Plant Physiology and Genetics, Bulgarian Academy of Sciences, Acad. G. Bonchev Street, Bldg. 21, 1113 Sofia, Bulgaria, E-mail:

Award Identifier / Grant number: KP-06-N43/6

  1. Research ethics: Not applicable.

  2. Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  4. Conflict of interest: The authors state no conflict of interest.

  5. Research funding: This work was funded by the Bulgarian National Science Fund, Ministry of Education and Science, grant number KP-06-N43/6 (КП-06-Н43/6/2020).

  6. Data availability: The raw data can be obtained on request from the corresponding author.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/znc-2024-0140).


Received: 2024-06-12
Accepted: 2024-09-10
Published Online: 2024-09-30
Published in Print: 2025-05-26

© 2024 Walter de Gruyter GmbH, Berlin/Boston

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