Anti-metastatic potential of flavonoids for the treatment of cancers: focus on epithelial-mesenchymal transition (EMT) process

Mohammad SI 1 , Vasudevan A 2 , Nadhim Mohammed S 3 , Uthirapathy S 4 , M M R 5 , Kundlas M 6 Show all authors , Siva Prasad GV 7 , Kumari M 8 , Mustafa YF 9 , Ali Hussein Z 10

Affiliations 

  • 1 Electronic Marketing and Social Media, Economic and Administrative Sciences Zarqa University, Zarqa, Jordan
  • 2 Faculty of Business and Communications, INTI International University, 71800, Negeri Sembilan, Malaysia
  • 3 Medical Laboratory Techniques Department, College of Health and Medical Technology, University of Al-Maarif, Anbar, Iraq. samia.nathim@uoa.edu.iq
  • 4 Pharmacy Department, Tishk International University, Erbil, Kurdistan Region, Iraq
  • 5 Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to Be University), Bangalore, Karnataka, India
  • 6 Centre for Research Impact & Outcome, Chitkara University Institute of Engineering and Technology, Chitkara University, Rajpura, 140401, Punjab, India
  • 7 Department of Chemistry, Raghu Engineering College, Visakhapatnam, Andhra Pradesh, 531162, India
  • 8 Department of Applied Sciences-Chemistry, NIMS Institute of Engineering & Technology, NIMS University Rajasthan, Jaipur, India
  • 9 Department of Pharmaceutical Chemistry, College of Pharmacy, University of Mosul, Mosul, 41001, Iraq
  • 10 Radiological Techniques Department, College of Health and Medical Techniques, Al-Mustaqbal University, 51001, Babylon, Iraq
Naunyn Schmiedebergs Arch Pharmacol, 2025 Nov;398(11):14849-14875.
PMID: 40434422 DOI: 10.1007/s00210-025-04235-3

Abstract

The leading factor contributing to patient mortality is the local invasion and metastasis of tumors, which are influenced by the malignant progression of tumor cells. The epithelial-mesenchymal transition (EMT) is key to understanding malignancy development. EMT is a critical regulatory mechanism for differentiating cell populations initially observed during the neural crest and embryonic gastrulation formation. This process is closely associated with tumor metastasis in cancer and is also related to the maintenance of cancer stem cells. Flavonoids, known for their antioxidant properties, have been widely studied for their anticancer potential to protect plants from harmful environmental conditions. They have attracted considerable attention and have been the focus of numerous experimental and epidemiological studies to evaluate their potential in cancer treatment. In vitro and in vivo research has demonstrated that flavonoids can significantly impact cancer-related EMT. They may inhibit the EMT process by reducing the levels of Twist1, N-cadherin, ZEB1, integrins, SNAI1/2, CD44, MMPs, and vimentin while increasing E-cadherin levels and targeting the PI3K/AKT, NF-κB p65, and JAK2/STAT3 signaling pathways. In order to suppress the transcription of the E-cadherin promoter, several Zn-finger transcription factors, such as SNAI2, ZEB1, and ZEB2, and basic helix-loop-helix (bHLH) factors, such as Twist, may directly bind to its E-boxes. Overall, clinical cancer research should integrate the anticancer properties of flavonoids, which address all phases of carcinogenesis, including EMT, to improve the prospects for targeted cancer therapies in patients suffering from aggressive forms of tumors.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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