title: Anticancer activity of Nigella sativa (black seed) and its relationship with the thermal processing and quinone composition of the seed.
abstract: The traditional preparation process of Nigella sativa (NS) oil starts with roasting of the seeds, an allegedly unnecessary step that was never skipped. The aims of this study were to investigate the role and boundaries of thermal processing of NS seeds in the preparation of therapeutic extracts and to elucidate the underlying mechanism. NS extracts obtained by various seed thermal processing methods were investigated in vitro for their antiproliferative activity in mouse colon carcinoma (MC38) cells and for their thymoquinone content. The effect of the different methods of thermal processing on the ability of the obtained NS oil to inhibit the nuclear factor kappa B (NF-κB) pathway was then investigated in Hodgkin's lymphoma (L428) cells. The different thermal processing protocols yielded three distinct patterns: heating the NS seeds to 50°C, 100°C, or 150°C produced oil with a strong ability to inhibit tumor cell growth; no heating or heating to 25°C had a mild antiproliferative effect; and heating to 200°C or 250°C had no effect. Similar patterns were obtained for the thymoquinone content of the corresponding oils, which showed an excellent correlation with the antiproliferative data. It is proposed that there is an oxidative transition mechanism between quinones after controlled thermal processing of the seeds. While NS oil from heated seeds delayed the expression of NF-κB transcription, non-heated seeds resulted in only 50% inhibition. The data indicate that controlled thermal processing of NS seeds (at 50°C-150°C) produces significantly higher anticancer activity associated with a higher thymoquinone oil content, and inhibits the NF-κB signaling pathway.
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Riad
authors.initials: R
authors.lastname: Agbaria
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Adi
authors.initials: A
authors.lastname: Gabarin
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Arik
authors.initials: A
authors.lastname: Dahan
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Shimon
authors.initials: S
authors.lastname: Ben-Shabat
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D016227:Benzoquinones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D004355:Drug Stability; D015972:Gene Expression Regulation, Neoplastic; D006689:Hodgkin Disease / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D006358:Hot Temperature; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D031881:Nigella sativa / Q000737:chemistry; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010938:Plant Oils / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D012639:Seeds; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection; D029974:Carum
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016227:Benzoquinones; D016328:NF-kappa B; D010936:Plant Extracts; D010938:Plant Oils; C104525:caraway oil; C003466:thymoquinone
keywords: NF-κB; Nigella sativa; antiproliferative effect; thermal processing; thymoquinone