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Black Cumin – A herb, a medicine for cancer treatment?

Cancer is one such condition wherein, additional adjuvants are always preferred in combination with the medical treatment in order to obtain the best possible result and to improve the quality of life of an individual at a short span of time interval. Researches and medical sciences have come a long way in treating cancer via inventing new technologies, administering new drugs, reducing the side effects and also keeping the treatments as painless as possible. As these have not yet gained complete confidence of the general public to eradicate cancer from one’s life, people are leaning towards the comfortable use of some natural herbs and ingredients along with the ongoing medications. One such ingredients are small, black colored, house hold spice – Black Cumin. Even-though it is named cumin, it has no relevance what so ever with the cumin (Jeerige or Jeera) used in our dishes.


Black cumin – scientific name: Nigella sativais a common household spice traditionally used in Indian and middle eastern cuisines. It is known for its medicinal properties which targets cancer, diabetes, hypertension and many more. One of its main components is: Thymoquinone along with carvone, limonene, citronellol and two varieties of alkaloids namely, isoquinoline and pyrazole. These seeds are composed of proteins, fat, carbohydrates, crude fibre, and total ash with proteins being in the highest concentration. Research suggests that black cumin could be potentially used as an effective agent in controlling tumor growth, metastasis either independently or in combination with other therapeutic drugs. This inference is due to the fact that black cumin has anti-cancer properties such as pro-apoptotic, anti-proliferative, cytotoxic, anti-metastatic and also is an anti-oxidant in many primary cancer cells and cancer cell lines.

Thymoquinone mostly targets the various cell cycle stages and acts as an anti-cancer component.


Fig. 1 Structural Representation of Thymoquinone

Apoptosis is a series of cellular events which results in cell death. It is an organized process where each and every step is meticulously carried out. cell cycle stages with functions.


Cell division is an essential part of cell to proliferation. To do so a cell needs to cross different stages with frequent check points. Cell cycle is divided into 4 stages namely, growth phase 1, synthesis phase, growth phase 2 and mitosis (G1, S, G2 and M). G1 phase is where the cell is prepared for duplication of DNA and centrioles along with the replication of chromosomes and histones synthesis. S phase is where the replication of DNA occurs and in G2 phase replication of RNA and proteins take place. There are checkpoints at each stage which checks for any defect in the cells and if any defective cells are found then they are not allowed any further and are digested. Certain non-dividing cells are sent to G0 phase where the cells are in their resting stage.



Fig. 2 Properties of Black Cumin

Thymoquinone as mentioned earlier has various positive effects on the human system and the details regarding the same is given below:


Anti-oxidative effects:

Thymoquinone increased the anti-oxidative properties by upregulating the anti-oxidative enzymes such as catalase (CAT), superoxide dismutase (SOD) as well as molecules such as glutathione (GSH). It also decreased the level of intracellular reactive oxygen species (ROS). This regulation was observed by the researchers in human SH-SY5Y cells where certain signaling genes such as extracellular signal-regulated protein kinase (ERK), p53, N-terminal kinase (JNK), protein kinase B (Akt1) along with nuclear- factor kappa-light-chain-enhancer of activated B cells were also involved. According to a meta-analysis study performed on 293 human subjects, black cumin may have some beneficial role in improving the SOD levels without affecting the total antioxidant capacity or the MDA level, which is an end product of lipid peroxidation that forms adduct by binding to DNA and also a biomarker of oxidative stress in cancer patients.


Bone Regenerative Effects:

Dental pulp mesenchymal stem cells (DP-MSCs) which were isolated from third molars of human patients between the age of 15-20 when incubated with NSO (oil from black cumin- Nigella sativa (NS) oil) indicated potential osteogenic differentiation as clear and compact calcium granules were observed. A clinical trial with 12 healthy patients was conducted with random division of patients into two groups (six in each). One group received the NS treatment while the other group did not, it was observed that the group which received the NS treatment showed an increase in the bone density which indicated improved bone quality.


Anti-Cancer Properties of thymoquinone in different types of cancers:

The property of regulating various cellular pathways which target cell proliferation, cell cycle regulation, apoptosis, carcinogenesis, angiogenesis and metastasis is very essential and the same can be achieved by thymoquinone. Regulation of cellular redox system mediates anti-cancer action (cell proliferation, migration or invasion, tumor growth by acting on certain growth factor signaling pathways like the Wnt, beta-catenine and so on) of thymoquinone. The enhancement of chemo sensitivity to chemotherapy and chemo-preventative molecules was achieved when thymoquinone down regulated inflammatory pathways and also by enhanced tumor suppressor genes.


LKB1 is a master kinase which phosphorylates and activates AMPK along with other kinases that play a major role in regulating cell growth and metabolism. LKB1-AMPK signaling is one which arrest cell growth under cellular ATP conditions, meaning, a surplus of energy may suppress this signaling hence promoting cancer risks specifically in patients with diabetes and obesity. In simple terms, if LKB1-AMPK signaling is suppressed then the risk of cancer is more and thymoqinone can activate this signaling which basically reduces the risk of cancer in an individual.


Human Cervical Cancer:

One of the researches where the extracts of Nigella sativa seeds was compared with the roots of Henidesmus indicus and rhizome of Glabra indicated that the former has the highest inhibitory effect on DNA synthesis. According to some studies Nigella sativa did show the pro-apoptotic gene expression by upregulating the pro-apoptotic gene Bcl2 which is associated with the X protein, down regulating the expression of anti-apoptotic Bcl2 gene and also showed enhanced activities of caspase 3 and 9 in time dependent manner. This infers that it can be used as a potential therapeutic medicinal plant for treatment of patients with cervical cancer. Studies done on human cervical cancer (SiHa cells) reported that the anti-cancer effect of Nigella sativa was linked to the increased expression of caspase 3,8 and 9 in several folds. Experiments conducted using solvent extracts like methanol, ethanol and chloroform indicated that these extracts could kill the human cervical carcinoma namely HeLa cells. The apoptotic function of ethanolic extract in particular was observed to be due to the association with the release of mitochondrial cytochrome c, increased Bax/Bcl 2 ratio, activation of caspase 3,9 and 8, increased expression of p53 and p21 along with reduced expressions of CDK-4 (Cyclin dependent kinase-4), human telomerase reverse transcriptase (hTERT) and many more. The same was confirmed in another paper where the experiment was conducted on human renal adenocarcinoma and normal renal epithelial cells.


Human Colorectal Cancer based on a Canine Osteosarcoma study:

In a study involving canine osteosarcoma, thymoquinone induced apoptosis in cells 6 hours after the treatment hence decreasing the number of cells in S phase and increasing the number of cells in G1 phase. When this concept was extrapolated in human colorectal cancer cells via a p53 dependent mechanism, it was observed that mRNA expression of p53 was increased up-to 2.5 to 4.5 folds along with a significant inhibition of Bcl2 proteins. There was also an analysis conducted using flow cytometry and TUNNEL method which interpreted the dose-and-time dependent arrest of cancer cells in the G1 phase indicating the correlation with canine osteosarcoma.


Human Breast Cancer:

With respect to human breast cancer specifically doxorubicin-resistant human breast cancer, inhibition of cell proliferation was observed due to various mechanism and they are as follows.


Akt is a known regulator for cell survival. A study conducted on the doxorubicin – resistant human breast cancer cell line (MCF-7/DOX) reported that the levels of phosphorylated Akt was substantially decreased due to the increase in cellular level of phosphatase and tensin homolog (PTEN) proteins and also increase in the PTEN mRNA. Adding on, the study also observed an increase in the subG1 cell stage along with increase in proteins such as p53 and p21. Other changes such as disruption of the mitochondrial membrane potential, increase in the Bax/Bcl ratio PARP cleavage and activation of caspases were also observed.


Some of the effects mentioned above were observed in many other cancer cell lines such as p53 – null HL-60 cell lines (myeloblastic leukemia), A549 (lung carcinoma), HT-29(colon adenocarcinoma), HEp-2(larynx epidermoid carcinoma), and MIA PaCa-2(pancreas carcinoma).


Intake:

Soak Black cumin seeds in water over night and have it first thing in the morning. The seeds can be consumed raw.





Black Cumin – A herb, a medicine for cancer treatment?

Cancer is one such condition wherein, additional adjuvants are always preferred in combination with the medical treatment in order to obtain the best possible result and to improve the quality of life of an individual at a short span of time interval. Researches and medical sciences have come a long way in treating cancer via inventing new technologies, administering new drugs, reducing the side effects and also keeping the treatments as painless as possible. As these have not yet gained complete confidence of the general public to eradicate cancer from one’s life, people are leaning towards the comfortable use of some natural herbs and ingredients along with the ongoing medications. One such ingredients are small, black colored, house hold spice – Black Cumin. Even-though it is named cumin, it has no relevance what so ever with the cumin (Jeerige or Jeera) used in our dishes.


Black cumin – scientific name: Nigella sativais a common household spice traditionally used in Indian and middle eastern cuisines. It is known for its medicinal properties which targets cancer, diabetes, hypertension and many more. One of its main components is: Thymoquinone along with carvone, limonene, citronellol and two varieties of alkaloids namely, isoquinoline and pyrazole. These seeds are composed of proteins, fat, carbohydrates, crude fibre, and total ash with proteins being in the highest concentration. Research suggests that black cumin could be potentially used as an effective agent in controlling tumor growth, metastasis either independently or in combination with other therapeutic drugs. This inference is due to the fact that black cumin has anti-cancer properties such as pro-apoptotic, anti-proliferative, cytotoxic, anti-metastatic and also is an anti-oxidant in many primary cancer cells and cancer cell lines.

Thymoquinone mostly targets the various cell cycle stages and acts as an anti-cancer component.


Fig. 1 Structural Representation of Thymoquinone

Apoptosis is a series of cellular events which results in cell death. It is an organized process where each and every step is meticulously carried out. cell cycle stages with functions.


Cell division is an essential part of cell to proliferation. To do so a cell needs to cross different stages with frequent check points. Cell cycle is divided into 4 stages namely, growth phase 1, synthesis phase, growth phase 2 and mitosis (G1, S, G2 and M). G1 phase is where the cell is prepared for duplication of DNA and centrioles along with the replication of chromosomes and histones synthesis. S phase is where the replication of DNA occurs and in G2 phase replication of RNA and proteins take place. There are checkpoints at each stage which checks for any defect in the cells and if any defective cells are found then they are not allowed any further and are digested. Certain non-dividing cells are sent to G0 phase where the cells are in their resting stage.



Fig. 2 Properties of Black Cumin

Thymoquinone as mentioned earlier has various positive effects on the human system and the details regarding the same is given below:


Anti-oxidative effects:

Thymoquinone increased the anti-oxidative properties by upregulating the anti-oxidative enzymes such as catalase (CAT), superoxide dismutase (SOD) as well as molecules such as glutathione (GSH). It also decreased the level of intracellular reactive oxygen species (ROS). This regulation was observed by the researchers in human SH-SY5Y cells where certain signaling genes such as extracellular signal-regulated protein kinase (ERK), p53, N-terminal kinase (JNK), protein kinase B (Akt1) along with nuclear- factor kappa-light-chain-enhancer of activated B cells were also involved. According to a meta-analysis study performed on 293 human subjects, black cumin may have some beneficial role in improving the SOD levels without affecting the total antioxidant capacity or the MDA level, which is an end product of lipid peroxidation that forms adduct by binding to DNA and also a biomarker of oxidative stress in cancer patients.


Bone Regenerative Effects:

Dental pulp mesenchymal stem cells (DP-MSCs) which were isolated from third molars of human patients between the age of 15-20 when incubated with NSO (oil from black cumin- Nigella sativa (NS) oil) indicated potential osteogenic differentiation as clear and compact calcium granules were observed. A clinical trial with 12 healthy patients was conducted with random division of patients into two groups (six in each). One group received the NS treatment while the other group did not, it was observed that the group which received the NS treatment showed an increase in the bone density which indicated improved bone quality.


Anti-Cancer Properties of thymoquinone in different types of cancers:

The property of regulating various cellular pathways which target cell proliferation, cell cycle regulation, apoptosis, carcinogenesis, angiogenesis and metastasis is very essential and the same can be achieved by thymoquinone. Regulation of cellular redox system mediates anti-cancer action (cell proliferation, migration or invasion, tumor growth by acting on certain growth factor signaling pathways like the Wnt, beta-catenine and so on) of thymoquinone. The enhancement of chemo sensitivity to chemotherapy and chemo-preventative molecules was achieved when thymoquinone down regulated inflammatory pathways and also by enhanced tumor suppressor genes.


LKB1 is a master kinase which phosphorylates and activates AMPK along with other kinases that play a major role in regulating cell growth and metabolism. LKB1-AMPK signaling is one which arrest cell growth under cellular ATP conditions, meaning, a surplus of energy may suppress this signaling hence promoting cancer risks specifically in patients with diabetes and obesity. In simple terms, if LKB1-AMPK signaling is suppressed then the risk of cancer is more and thymoqinone can activate this signaling which basically reduces the risk of cancer in an individual.


Human Cervical Cancer:

One of the researches where the extracts of Nigella sativa seeds was compared with the roots of Henidesmus indicus and rhizome of Glabra indicated that the former has the highest inhibitory effect on DNA synthesis. According to some studies Nigella sativa did show the pro-apoptotic gene expression by upregulating the pro-apoptotic gene Bcl2 which is associated with the X protein, down regulating the expression of anti-apoptotic Bcl2 gene and also showed enhanced activities of caspase 3 and 9 in time dependent manner. This infers that it can be used as a potential therapeutic medicinal plant for treatment of patients with cervical cancer. Studies done on human cervical cancer (SiHa cells) reported that the anti-cancer effect of Nigella sativa was linked to the increased expression of caspase 3,8 and 9 in several folds. Experiments conducted using solvent extracts like methanol, ethanol and chloroform indicated that these extracts could kill the human cervical carcinoma namely HeLa cells. The apoptotic function of ethanolic extract in particular was observed to be due to the association with the release of mitochondrial cytochrome c, increased Bax/Bcl 2 ratio, activation of caspase 3,9 and 8, increased expression of p53 and p21 along with reduced expressions of CDK-4 (Cyclin dependent kinase-4), human telomerase reverse transcriptase (hTERT) and many more. The same was confirmed in another paper where the experiment was conducted on human renal adenocarcinoma and normal renal epithelial cells.


Human Colorectal Cancer based on a Canine Osteosarcoma study:

In a study involving canine osteosarcoma, thymoquinone induced apoptosis in cells 6 hours after the treatment hence decreasing the number of cells in S phase and increasing the number of cells in G1 phase. When this concept was extrapolated in human colorectal cancer cells via a p53 dependent mechanism, it was observed that mRNA expression of p53 was increased up-to 2.5 to 4.5 folds along with a significant inhibition of Bcl2 proteins. There was also an analysis conducted using flow cytometry and TUNNEL method which interpreted the dose-and-time dependent arrest of cancer cells in the G1 phase indicating the correlation with canine osteosarcoma.


Human Breast Cancer:

With respect to human breast cancer specifically doxorubicin-resistant human breast cancer, inhibition of cell proliferation was observed due to various mechanism and they are as follows.


Akt is a known regulator for cell survival. A study conducted on the doxorubicin – resistant human breast cancer cell line (MCF-7/DOX) reported that the levels of phosphorylated Akt was substantially decreased due to the increase in cellular level of phosphatase and tensin homolog (PTEN) proteins and also increase in the PTEN mRNA. Adding on, the study also observed an increase in the subG1 cell stage along with increase in proteins such as p53 and p21. Other changes such as disruption of the mitochondrial membrane potential, increase in the Bax/Bcl ratio PARP cleavage and activation of caspases were also observed.


Some of the effects mentioned above were observed in many other cancer cell lines such as p53 – null HL-60 cell lines (myeloblastic leukemia), A549 (lung carcinoma), HT-29(colon adenocarcinoma), HEp-2(larynx epidermoid carcinoma), and MIA PaCa-2(pancreas carcinoma).


Intake:

Soak Black cumin seeds in water over night and have it first thing in the morning. The seeds can be consumed raw.





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