Parthenolide reverses the epithelial to mesenchymal transition process in breast cancer by targeting TGFbeta1: In vitro and in silico studies

Hazera Binte Sufian, Julianna Maria Santos, Zeina S. Khan, Sobia Ahsan Halim, Ajmal Khan, Maliha Tabassum Munir, MD Khurshidul Zahid, Ahmed Al-Harrasi, Lauren S. Gollahon, Fazle Hussain, Shaikh Mizanoor Rahman

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Aims: Breast cancer metastasis is the leading cause of mortality among breast cancer patients. Epithelial to mesenchymal transition (EMT) is a biological process that plays a fundamental role in facilitating breast cancer metastasis. The present study assessed the efficacy of parthenolide (PTL Tanacetum parthenium) on EMT and its underlying mechanisms in both lowly metastatic, estrogen-receptor positive, MCF-7 cells and highly metastatic, triple-negative MDA-MB-231 cells. Main methods: MCF-7 and MDA-MB-231 cells were treated with PTL (2 μM and 5 μM). Cell viability was determined by MTT (3-(4,5-dimethy lthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. Apoptosis was analyzed by the FITC (fluorescein isothiocyanate) annexin V apoptosis detection kit. The monolayer wound scratch assay was employed to evaluate cancer cell migration. Proteins were separated and identified by Western blotting. Gene expression was analyzed by quantitative real-time PCR. Key findings: PTL treatment significantly reduced cell viability and migration while inducing apoptosis in both cell lines. Also, PTL treatment reverses the EMT process by decreasing the mesenchymal marker vimentin and increasing the epithelial marker E-cadherin compared to the control treatment. Importantly, PTL downregulates TWIST1 (a transcription factor and regulator of EMT) gene expression, concomitant with the reduction of transforming growth factor beta1 (TGFβ1) protein and gene expression in both cell lines. Additionally, molecular docking studies suggest that PTL may induce anticancer properties by targeting TGFβ1 in both breast cancer cell lines. Significance: Our findings provide insights into the therapeutic potential of PTL to mitigate EMT and breast cancer metastasis. These promising results demand in vivo studies.

Original languageEnglish (US)
Article number120610
JournalLife sciences
Volume301
DOIs
StatePublished - Jul 15 2022

Keywords

  • Breast cancer
  • EMT
  • Metastasis
  • Molecular docking
  • Parthenolide
  • Transcription factor

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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