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

Molecules

卷:27

Mahmoud Alhosin¹  Safialdin Alsanosi¹  Ryan A. Sheikh¹  Sultan Sonbul¹  Salman Hosawi¹  Hisham N. Altayb¹  Afnan S. Batubara²  Omeima Abdullah²  Ziad Omran³  Kaltoom Al-Sakkaf⁴ 

[1] Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia;

[2] College of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia;

[3] Department of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, Jeddah 21442, Saudi Arabia;

[4] Medical Laboratory Technology Department, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia;

关键词: Nigella sativa oil;    thymoquinone;    epigenetic;    cancer;    UHRF1;    DNMT1;   

DOI  :  10.3390/molecules27092779

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown