The Potential Role of Nigella sativa Seed Oil as Epigenetic Therapy of Cancer.
Safialdin AlsanosiRyan Adnan SheikhSultan SonbulHisham N AltaybAfnan S BatubaraSalman B HosawiKaltoom Al-SakkafOmeima AbdullahZiad OmranMahmoud AlhosinPublished in: Molecules (Basel, Switzerland) (2022)
Nigella sativa oil, commonly known as black seed oil (BSO), is a well-known Mediterranean food, and its consumption is associated with beneficial effects on human health. A large number of BSO's therapeutic properties is attributed to its pharmacologically active compound, thymoquinone (TQ), which inhibits cell proliferation and induces apoptosis by targeting several epigenetic players, including the ubiquitin-like, containing plant homeodomain (PHD) and an interesting new gene, RING finger domains 1 (UHRF1), and its partners, DNA methyltransferase 1 (DNMT1) and histone deacetylase 1 (HDAC1). This study was designed to compare the effects of locally sourced BSO with those of pure TQ on the expression of the epigenetic complex UHRF1/DNMT1/HDAC1 and the related events in several cancer cells. The gas chromatographs obtained from GC-MS analyses of extracted BSO showed that TQ was the major volatile compound. BSO significantly inhibited the proliferation of MCF-7 , HeLa and Jurkat cells in a dose-dependent manner, and it induced apoptosis in these cell lines. BSO-induced inhibitory effects were associated with a significant decrease in mRNA expression of UHRF1, DNMT1 and HDAC1. Molecular docking and MD simulation showed that TQ had good binding affinity to UHRF1 and HDAC1. Of note, TQ formed a stable metal coordinate bond with zinc tom, found in the active site of the HDAC1 protein. These findings suggest that the use of TQ-rich BSO represents a promising strategy for epigenetic therapy for both solid and blood tumors through direct targeting of the trimeric epigenetic complex UHRF1/DNMT1/ HDAC1.
Keyphrases
- histone deacetylase
- dna methylation
- induced apoptosis
- genome wide
- human health
- gene expression
- molecular docking
- signaling pathway
- endoplasmic reticulum stress
- cell proliferation
- risk assessment
- oxidative stress
- copy number
- fatty acid
- binding protein
- transcription factor
- cell cycle arrest
- poor prognosis
- breast cancer cells
- small molecule
- climate change
- papillary thyroid
- bone marrow
- cell death
- nucleic acid
- diabetic rats
- young adults
- cell free
- gas chromatography
- dna binding
- cell cycle
- cell therapy
- squamous cell
- mesenchymal stem cells