Repurposing mebendazole to reprogram oncogenic and tumor-suppressor networks: Multi-cancer insights from ENOX2, MMP2,

Rasha Shaker Aqel1, Areej Sami Ismail1, Mohamed El-Tanani2

  • 1Faculty of Pharmacy, Al-Ahliyya Amman University, Amman, Jordan.

Plos One
|March 26, 2026
PubMed
Abstract

Insights

Mebendazole reprograms cancer cell networks by downregulating oncogenes ENOX2 and MMP2, and upregulating tumor suppressors RASSF1A and WFDC10A, showing potential as an anticancer agent.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Repurposing

Background:

  • Cancer progression involves complex regulation of oncogenes and tumor suppressors.
  • This study investigates the interplay of ENOX2, MMP2, RASSF1A, WFDC10A, and METTL7A in various cancer cell lines.
  • The anticancer potential of repurposed mebendazole is evaluated.

Purpose of the Study:

  • To explore the regulatory network of specific oncogenes and tumor suppressors in cancer.
  • To assess the impact of mebendazole on these regulatory genes.
  • To identify potential biomarkers for cancer diagnosis and therapy.

Main Methods:

  • Utilized qRT-PCR and Western blotting to profile eight human cancer cell lines.
  • Assessed gene expression under basal conditions and after mebendazole treatment (0.7 µM).

Main Results:

  • Elevated ENOX2 and MMP2 were observed in aggressive cancer cell lines.
  • Mebendazole significantly downregulated ENOX2 and MMP2, indicating anti-invasive effects.
  • Tumor suppressors RASSF1A and WFDC10A were selectively induced by mebendazole, with cell-type-specific modulation observed for METTL7A.

Conclusions:

  • ENOX2-MMP2 signaling drives invasion and metastasis in cancer.
  • Mebendazole effectively reprograms oncogenic-tumor suppressor networks.
  • Mebendazole shows translational potential as a cost-effective anticancer agent, supporting multi-gene biomarker development for aggressive malignancies.

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