Black seed oil (Nigella sativa) and its thymoquinone are effective against breast cancer and other malignancies

Black  seed oil  (Nigella sativa) can be a safe, cost-friendly and  effective adjunctive therapy for breast cancer and other malignancies. Notwithstanding the lack of clinical trials data, there nonetheless is  evidence that does support the claim that  black cumin seed oil and its extract thymoquinone have benefits for various inflammatory diseases including, but not limited to liver cancer, melanoma skin cancer, pancreatic cancer, cervical cancer, breast cancer, bone cancer, stomach cancer, lymphoma, prostate cancer, colon cancer, and brain cancer.  (1)  Among others,  Chinese researchers (2)  noted that black seed oil has been used as a traditional medicine for centuries.  This annual herb grows in countries bordering the Mediterranean Sea and India.

BIOLOGICAL MECHANISMS OF ACTION

The scientific litterature shows tha there has been over 600 published, peer-reviewed studies referencing it concerning over 40 health conditions that may be benefited from the use of the herb, including over 20 distinct biological mechanisms of actions it expresses from anti inflammatory to being an antioxidant, antiviral, insulin sensitizer, interferon inducer, gluconeogenesis inhibitor, leukotriene antagonist, renoprotective pathways, tumor necrosis factor alpha inhibitor, mitigator of antibiotic resistant bacteria,  detoxification of poisons, stimulation of dying insulin-producing beta cells in the diabetic’s pancreas etc, among other pathways.

This shows that this seed-plant, like ginger, ginseng, tumeric, grapeseed, pumpkin seed are highly complex substances that favorably  modulate many different biological pathways synergistically, which makes this seed a truely holistic one.

SUPPORTING EVIDENCE

In 2013, researchers investigated the use of thymoquinone via two groups of rats with liver cancer were studied. One group was given water to drink that contained 0.01% thymoquinone, and the other group was given plain water. After 16 weeks, the liver cancer nodules, liver injury markers and tumor markers were measured in both groups. The rats that did not receive the thymoquinone had substantial increases in liver tumor size. However, the rats that received 20 mg of thymoquinone per kilogram for body weight had greatly reduced liver injury markers and decreased tumor markers. The group treated with thymoquinone from black seed oil did not develop liver cancer nodules, and the amount of new tumor formation was much less than the untreated group of rats. They concluded that thymoquinone had a beneficial role in the treatment of liver cancer, because of its potent ability to prevent cancer cells from proliferating. (3)  It also controls the Akt pathway, which means it controls the process that manages cell survival for both normal and cancer cells

A 2012 study from Egypt evaluated anti-tumor effects of bee honey and black seed oil on human liver cancer cells in laboratory experiments. They examined the antioxidant capacity of honey and black seed extract, and the ability of these substances to eliminate unhealthy cells such as cancer. They found that both honey and black seed extract were effective in reducing the viability of liver cancer cells. Honey and black seed extract also improved the antioxidant status of cells and induced cancer cell death by apoptosis. (4)

 Another study investigated the anti-cancer activity of black seed oil and black seed extract when used against human lung cancer cells in the laboratory. Scientists exposed lung cancer cells to black seed oil or to black seed extract for 24 hours. They used 0.01 mg/ml to 1 mg/ml of the oil or the extract in this experiment. After the exposure, the cancer cell viability was assessed. The results showed that both the black seed oil and the black seed extract significantly reduce the population of living cancer cells and altered the cellular morphology. They found that the greater the concentration of the oil or the extract that was used to treat the cancer cells, the greater the level of cell death. Also, both the black seed oil and the black seed extract caused the cancer cells to lose their typical appearance and to appear smaller in size. Researchers concluded that their data revealed that black seed extract and black seed oil significantly reduce viability of human lung cancer cells. (5).

Researchers from Ohio State University examined how thymoquinone selectively inhibits the ability of glioblastoma cancer cells of the brain and spinal cord from making clones of themselves. Thymoquinone, however, does not inhibit normal cell activity in the human brain and spinal cord. Another important ability of thymoquinone is the inhibition of autophagy genes in cancer cells. Autophagy in cancer cells enables continued growth of tumor cells by maintaining cellular energy production. If autophagy is inhibited, then cellular energy production for cancer cells will also be inhibited. This will result in a regression of tumor activity, and will extend the survival of organs affected by tumors. Thus, thymoquinone’s ability to inhibit cancer cells from making clones of themselves and its ability to inhibit cancer cells from reusing cellular materials from other cells by means of autophagy, provide an exciting and emerging strategy for cancer therapy. (6)

A 2013 study addressed the anti-cancer efficiency of thymoquinone when it was used for long-term treatment of human breast cancer cell lines in the laboratory. Thymoquinone showed a sustained ability to inhibit breast cancer cell proliferation with long-term treatment. The length of inhibition was determined by the size of the thymoquinone dose. Larger doses produced greater inhibition. (7)

The anti-cancer effect of thymoquinone, via the induction of apoptosis resulting from mitochondrial dysfunction, was assessed in an acute leukemia cell line. Researchers found that treatment of leukemia cells with thymoquinone encouraged apoptosis resulting in cell death. These results indicate that thymoquinone from black seeds could be a promising agent for the treatment of leukemia. (8)

In yet another study, researchers from the University of Mississippi Medical Center studied epigallocatechin-3-gallate, the key catechin found in green tea and thymoquinone in order to investigate the role of sustained delivery of thymoquinone from black seeds, catechin from green tea, and the chemotherapy drug 5-FU on the metabolic activity and the structural changes in human colon cancer cells in laboratory cultures. Results of this study showed that green tea catechin and black seed thymoquinone produced significant cancer cell destruction and interfered with cellular metabolic functions, which was comparable to cells exposed to sustained drug delivery of the chemotherapy drug 5-FU. Morphologically, cellular changes occurred after exposure to green tea catechin and thymoquinone for 24 hours, which was comparable to the cellular changes seen in cells exposed to the chemotherapy drug 5-FU. Ultimately, the researchers concluded that the natural agents may offer a safe alternative treatment for colon cancer. (9) (10) Equally supportive, animal research has found that black seed oil has significant inhibitory effects against colon cancer in rats, without observable side effects. (11)

BLACK SEED OIL HELPS TO MITIGATE THE EFFECTS OF RADIATION AND CHEMO

In a 2014 study, Turkish study investigated the effects of irradiation and the addition of black seed oil on the oxidant/antioxidant system in the liver tissue of irradiated rats. They exposed some of the rats to a single dose of gamma radiation. One group of rats received one gram of black seed oil per kilogram of body weight one hour before the radiation and received a daily dose afterward for 10 days. Another group received the radiation treatment and was given a saline solution instead of black seed oil. The control group was not irradiated. The analysis of the data shows that black seed oil reduces oxidative stress markers and has antioxidant effects, which also augments the antioxidant capacity in the liver tissue of rats. Thus, the use of black seed oil before radiation treatment, and for 10 days afterward, protected the rats from some of the harmful effects of radiation. (12)

In a 2012 study, scientists investigated the effect of using an extract of black seeds on mice exposed to gamma radiation. A group of normal mice and a group of tumor bearing mice were tested. This experiment was done to mimic the human clinical setting where normal tissues of cancer patients are exposed to the harmful effects of radiation therapy. The mice were given black seed extract before being exposed to the gamma radiation. They were given 100 mg of black seed extract per 1 kg of body weight. The results showed that the extract of black seed protected the liver, spleen, brain and intestines from gamma radiation damage for both the normal mice and the mice with tumors. Researchers concluded that the liquid extract of black seeds has protective effects against radiation-induced damage and biochemical alterations. They attributed this protective effect to the ability of the extract to scavenge free radicals and to its antioxidant properties. Thus, the liquid extracted from black seeds could be used with human cancer patients who receive radiation to protect against oxidative stress in normal tissues, and to mitigate other unwanted side effects of radiation. This could improve the quality of life for cancer patients. (13)

In 2011, German researchers described the drug doxorubicin as being a mainstay of cancer chemotherapy despite its cardiotoxicity and its limited ability to treat multi-drug resistant cancers. Recent studies revealed a protective effect of thymoquinone, a non-toxic constituent of the essential oil of Nigella sativa, against doxorubicin-induced cardiotoxicity. In summary, they found that thymoquinone is a booster for the anti-cancer effect of the chemotherapy agent doxorubicin in certain cancer cell lines. (14)

In 2013, researchers from Singapore reported that there are a limited number of therapeutic agents for cancer, and cancer cells are developing resistance to these agents. Thus, there is a need to discover novel agents to treat breast cancer. The antitumor activities of thymoquinone, a compound isolated from black seed oil, were used to treat mice with breast cancer. Thymoquinone treatment was found to suppress tumor growth, and this effect was further enhanced by combining it with the chemotherapy drug doxorubicin. (15)

CONCLUSION: BEES AND BLACK SEEDS

Researchers studied the protective effect of bee honey and Nigella grains on the oxidative stress and the cancer that was created by exposing rats to a strong carcinogen. After the four groups of rats were exposed to the carcinogen, some groups were fed black seeds or honey, and one group was fed both black seeds and honey. The rats were evaluated after 6 months. The rats that ate black seeds received an 80% protection against oxidative stress and cancer formation. Whereas the rats that ate a daily dose of both honey and black seeds were protected 100% against oxidative stress, inflammatory responses, and cancer formation. (16)

Black Seeds can have many beneficial uses from Helicobacter pylori and mrsa infection   to cancer, as we have seen, to many others, even asthma.  (17)   From the experience of black seed experts, 1 to 3 teaspoons of black seed oil per day for various conditions is usually indicated. One teaspoon seems to be a daily dose to support health.  With honey, the effects appear to be potentiated.

Pr. Joubert (ACR Institute Director)

References

(1). Woo CC1, Kumar AP, Sethi G, Tan KH.; “Thymoquinone: potential cure for inflammatory disorders and cancer,” Biochem Pharmacol. 2012.

(2).  Khan MA1, Chen HC, Tania M, Zhang DZ.; “Anticancer activities of Nigella sativa (black cumin),” Afr J Tradit Complement Altern Med. 2011, PMID: 22754079.

(3).  Raghunandhakumar S1, Paramasivam A, Senthilraja S, Naveenkumar C, Asokkumar S, Binuclara J, Jagan S, Anandakumar P, Devaki T.; “Thymoquinone inhibits cell proliferation through regulation of G1/S phase cell cycle transition in N-nitrosodiethylamine-induced experimental rat hepatocellular carcinoma,” Toxicol Lett. 2013 Oct 23, PMID: 24012840.

(4).  Hassan MI1, Mabrouk GM, Shehata HH, Aboelhussein MM.; “Antineoplastic effects of bee honey and Nigella sativa on hepatocellular carcinoma cells,” Integr Cancer Ther. 2012 Dec, PMID: 21147814.

(5). Al-Sheddi ES1, Farshori NN, Al-Oqail MM, Musarrat J, Al-Khedhairy AA, Siddiqui MA.; “Cytotoxicity of Nigella sativa seed oil and extract against human lung cancer cell line,” Asian Pac J Cancer Prev. 2014, PMID: 24568529.

(6).  Racoma IO1, Meisen WH, Wang QE, Kaur B, Wani AA.; “Thymoquinone inhibits autophagy and induces cathepsin-mediated, caspase-independent cell death in glioblastoma cells,” PLoS One. 2013 Sep 9, PMID: 24039814.

(7). Motaghed M1, Al-Hassan FM, Hamid SS.; “Cellular responses with thymoquinone treatment in human breast cancer cell line MCF-7,” Pharmacognosy Res. 2013 Jul, PMID: 23900121.

(8). Salim LZ1, Mohan S, Othman R, Abdelwahab SI, Kamalidehghan B, Sheikh BY, Ibrahim MY.; “Thymoquinone induces mitochondria-mediated apoptosis in acute lymphoblastic leukaemia in vitro,” Molecules. 2013 Sep 12, PMID: 24036512.

(9). Norwood AA1, Tucci M, Benghuzzi H; “A comparison of 5-fluorouracil and natural chemotherapeutic agents, EGCG and thymoquinone, delivered by sustained drug delivery on colon cancer cells,” Biomed Sci Instrum., 2007, PMID: 17487093.

(10).  Mohammad H Boskabady, Javad Farhadi. The possible prophylactic effect of Nigella sativa seed aqueous e(xtract on respiratory symptoms and pulmonary function tests on chemical war victims: a randomized, double-blind, placebo-controlled trial. J Altern Complement Med. 2008 Nov;14(9):1137-44. PMID: 18991514

(11).  Elsayed I Salim, Shoji Fukushima. Chemopreventive potential of volatile oil from black cumin (Nigella sativa L.) seeds against rat colon carcinogenesis. Nutr Cancer. 2003;45(2):195-202. PMID: 12881014

(12)  Cikman O1, Ozkan A, Aras AB, Soylemez O, Alkis H, Taysi S, Karaayvaz M.; “Radioprotective Effects of Nigella Sativa Oil Against Oxidative Stress in Liver Tissue of Rats Exposed to Total Head Irradiation,” J Invest Surg. 2014 Mar 28, PMID: 24679182.

(13)  Velho-Pereira R1, Kumar A, Pandey BN, Mishra KP, Jagtap AG.; “Radioprotection by Macerated Extract of Nigella sativa in Normal Tissues of Fibrosarcoma Bearing Mice,” Indian J Pharm Sci. 2012 Sep, PMID: 23716868.

 (14) Effenberger-Neidnicht K1, Schobert R.; “Combinatorial effects of thymoquinone on the anti-cancer activity of doxorubicin,” Cancer Chemother Pharmacol. 2011 April, PMID: 20582416.

[15] Gali-Muhtasib H1, Diab-Assaf M, Boltze C, Al-Hmaira J, Hartig R, Roessner A, Schneider-Stock R.; “Thymoquinone extracted from black seed triggers apoptotic cell death in human colorectal cancer cells via a p53-dependent mechanism,” Int J Oncol., 2004 October, PMID: 15375533.

[16] Salem EM1, Yar T, Bamosa AO, Al-Quorain A, Yasawy MI, Alsulaiman RM, Randhawa MA.; “Comparative study of Nigella Sativa and triple therapy in eradication of Helicobacter Pylori in patients with non-ulcer dyspepsia,” Saudi J Gastroenterol. 2010 Jul-Sep, PMID: 20616418.

(17). Thymoquinone has been shown to be superior to the drug fluticasone in an animal model of asthma. (cf.  Rana Keyhanmanesh, Mohammad Hossein Boskabady, Mohammad Javad Eslamizadeh, Saeed Khamneh, Mohammad Ali Ebrahimi. The effect of thymoquinone, the main constituent of Nigella sativa on tracheal responsiveness and white blood cell count in lung lavage of sensitized guinea pigs. J Ethnopharmacol. 2009 Oct 29;126(1):102-7). Another study, this time in human subjects, found that boiled water extracts of black seed have relatively potent anti-asthmatic effect on asthmatic airways. (cf M H Boskabady, N Mohsenpoor, L Takaloo . Antiasthmatic effect of Nigella sativa in airways of asthmatic patients. Phytomedicine. 2010 Feb 8).  For detoxification and chest relief, boiled water extracts of black seed appeared to be the best reduced respiratory symptoms, chest wheezing, and pulmonary function test values, as well as reduced the need for drug treatment.

 EXHIBIT A

PLoS One. 2013 Oct 2;8(10):e75356.

Thymoquinone inhibits tumor growth and induces apoptosis in a breast cancer xenograft mouse model: the role of p38 MAPK and ROS.

Woo CC1, Hsu A, Kumar AP, Sethi G, Tan KH

Abstract

Due to narrow therapeutic window of cancer therapeutic agents and the development of resistance against these agents, there is a need to discover novel agents to treat breast cancer. The antitumor activities of thymoquinone (TQ), a compound isolated from Nigella sativa oil, were investigated in breast carcinoma in vitro and in vivo. Cell responses after TQ treatment were assessed by using different assays including MTT assay, annexin V-propidium iodide staining, Mitosox staining and Western blot. The antitumor effect was studied by breast tumor xenograft mouse model, and the tumor tissues were examined by histology and immunohistochemistry. The level of anti-oxidant enzymes/molecules in mouse liver tissues was measured by commercial kits. Here, we show that TQ induced p38 phosphorylation and ROS production in breast cancer cells. These inductions were found to be responsible for TQ’s anti-proliferative and pro-apoptotic effects. Moreover, TQ-induced ROS production regulated p38 phosphorylation but not vice versa. TQ treatment was found to suppress the tumor growth and this effect was further enhanced by combination with doxorubicin. TQ also inhibited the protein expression of anti-apoptotic genes, such as XIAP, survivin, Bcl-xL and Bcl-2, in breast cancer cells and breast tumor xenograft. Reduced Ki67 and increased TUNEL staining were observed in TQ-treated tumors. TQ was also found to increase the level of catalase, superoxide dismutase and glutathione in mouse liver tissues. Overall, our results demonstrated that the anti-proliferative and pro-apoptotic effects of TQ in breast cancer are mediated through p38 phosphorylation via ROS generation.

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