The Potential Role of Nigella sativa Seed Oil as Epigenetic Therapy of Cancer

Abstract

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.

Common Applications of Black Cumin Seed (Nigella sativa) Oil in Folk Medicine

“…Cancer is triggered by a number of causes, including aberrant DNA methylation 188 , histone deacetylation 189 as well as genetic abnormalities 190 . Different tumor suppressor genes (TSGs) are silenced in cancer as a result of these epigenetic alterations 191 . Another carcinogenic causes is the free radicals build up in the body which produce oxidative stress and inducing carcinogenesis 192 .…”

In Vitro and In Vivo Preventive Effects of Thymoquinone against Breast Cancer: Role of DNMT1

“…For example, epigallocatechin-3-gallate (EGCG) [ 19 , 20 ] and curcumin [ 21 , 22 ] have anticancer activities related to their effects on DNA methylation and subsequent inhibition of the enzymatic activity and/or transcription of DNMT1. Another compound, thymoquinone (TQ), the biologically active component of black cumin ( Nigella sativa ) seeds, also shows cytotoxicity activities against various human cancer cells by targeting several signaling pathways, including the epigenetic machinery [ 23 , 24 , 25 , 26 , 27 ]. Several in vitro studies have shown that TQ has inhibitory effects on leukemia, a hematological tumor model, by inhibiting DNMT1 activity [ 28 ] and decreasing its expression at both the transcriptional and protein levels [ 25 , 27 , 29 , 30 ].…”