Luteolin Causes 5 ' CpG Demethylation of the Promoters of TSGs and Modulates the Aberrant Histone Modifications, Restoring the Expression of TSGs in Human Cancer Cells


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Pramodh S., Raina R., Hussain A., Bagabir S. A. , Haque S., Raza S. T. , ...More

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, vol.23, no.7, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 23 Issue: 7
  • Publication Date: 2022
  • Doi Number: 10.3390/ijms23074067
  • Journal Name: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, CAB Abstracts, EMBASE, Food Science & Technology Abstracts, MEDLINE, Veterinary Science Database, Directory of Open Access Journals
  • Keywords: DNA methylation, luteolin, antiproliferation, antimigration, histone modification, TUMOR-SUPPRESSOR GENES, INTRINSIC SIGNALING PATHWAYS, BREAST-CANCER, DNA METHYLTRANSFERASES, DIETARY POLYPHENOLS, INHIBITION, CHEMOPREVENTION, MECHANISMS, EPIGENOME, KINASE
  • Bursa Uludag University Affiliated: No

Abstract

Cancer progression is linked to abnormal epigenetic alterations such as DNA methylation and histone modifications. Since epigenetic alterations, unlike genetic changes, are heritable and reversible, they have been considered as interesting targets for cancer prevention and therapy by dietary compounds such as luteolin. In this study, epigenetic modulatory behaviour of luteolin was analysed on HeLa cells. Various assays including colony forming and migration assays, followed by biochemical assays of epigenetic enzymes including DNA methyltransferase, histone methyl transferase, histone acetyl transferase, and histone deacetylases assays were performed. Furthermore, global DNA methylation and methylation-specific PCR for examining the methylation status of CpG promoters of various tumour suppressor genes (TSGs) and the expression of these TSGs at transcript and protein level were performed. It was observed that luteolin inhibited migration and colony formation in HeLa cells. It also modulated DNA methylation at promoters of TSGs and the enzymatic activity of DNMT, HDAC, HMT, and HAT and reduced the global DNA methylation. Decrease in methylation resulted in the reactivation of silenced tumour suppressor genes including FHIT, DAPK1, PTEN, CDH1, SOCS1, TIMPS, VHL, TP53, TP73, etc. Hence, luteolin-targeted epigenetic alterations provide a promising approach for cancer prevention and intervention.