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GOLDEN SPICE for cancer - CURCUMIN

Turmeric also called as “THE GOLDEN SPICE”, is also termed as “Indian Saffron” due to its brilliant yellow color. The use of turmeric goes back to nearly 4000 years to Vedic culture in India, where it was used as culinary spice, for medicinal purposes and had religious significance, as its major source as curcumin. Curcumin (Diferuloylmethane) belongs to the class of polyphenols extracted from the rhizomes of Curcuma longa. This predominant natural ingredient is used worldwide for its biological properties like antioxidant, anti-inflammatory, antimicrobial, antiviral among which its anticancer potential has been the most described and remains under study till date.



Time and again, literature proves that the multiple beneficiary and medicinal properties of this curcumin (polyphenol content in turmeric) can be of great advantage to increase the wellbeing of an individual. Notably a few factors also help in preventing the further multiplication and spread of the cancer cells both in localized region as well as distant regions (in case of metastasis). These collective properties of curcumin make it a suitable option to be a vital ingredient to be included in the diet of patients undergoing treatment for various types of cancers to increase the quality of their life and can be continued during post-treatment period as well.


Curcumin has been reported to regulate transcription factors, growth factors, enzymes, kinase, inflammatory cytokines, and proapoptotic by up-regulation and anti-apoptotic by down-regulation proteins. This polyphenol compound, alone or combined with other agents could be represented one of the most effective drugs for cancer therapy.


Inflammation is a process by which body activates the immune system to protect the body from infection from outside invaders, such as bacteria and viruses. Inflammation can classified into short-lived (acute) or long-lasting (chronic). Acute inflammation goes away by few hours. Chronic inflammation can last for some months or even few years, even after the first trigger is gone.


The studies have shown that inflammation is a critical component of tumour progression. Many cancers originate from sites of infection, chronic irritation, as well as inflammation. It is understood that the tumour microenvironment is largely brought about by the inflammatory cells, is a crucial participant in the neoplastic process, fostering proliferation, survival and migration. The tumour cells have adopted some of the signaling molecules of the innate immune system, such as selectins, chemokines and their receptors for invasion, migration and metastasis (spread of cancer cells from the origin to different parts of the body).


The inflammation process brings about an increased production of pro-inflammatory molecules such as cytokines, ROS, cyclooxygenase (COX-2), transcription factors including nuclear factor κB (NF-κB), protein kinases B (AKT), activator protein 1 (AP1), signal transducer and activator of signal transducer and activator of transcription 3 (STAT3), causing the initiation and development of cancer.


Curcumin exerts its immunomodulatory ability by interacting with immune mediators (They mediate and regulate immune responses, inflammatory reactions, wound healing, hematopoiesis, and chemotaxis. Examples: Interleukins, Chemokines and lymphocytes). Hence, its anticancer property.


  • Nuclear factor κB is a pro-inflammatory transcription factor that regulate the expression of different proteins—such as cytokines interleukin-1 (IL-1), interleukin-1 (IL-2), and interferon-γ (IFNγ)—involved in multiple cell signaling pathways associated with cancer progression and inflammation. Phosphorylated NF-κB binds DNA and starts the transcription of oncogenes which block apoptosis and initiates cellular proliferation (Cell proliferation is the process by which a cell grows and divides to produce two daughter cells. Cell proliferation leads to and rapidly increase in cell number and is therefore a fast mechanism of tissue growth) and angiogenesis (Tumour angiogenesis is the growth of new blood vessels that tumours need for its further grow. The process is caused by the release of chemicals by the tumour). Curcumin suppress NF-κB activity by slowing down the phosphorylation by I kappa B kinase (IκB) and disrupt nuclear translocation of the NF-κB p65 subunit.


  • The Transcriptional factor AP-1 (Activator Protein-1) is related to anti-apoptotic (prevents apoptosis), mitogenic (provides selective growth for cells that have initiated mitosis), and pro-angiogenic genes, is downregulated by curcumin. Curcumin is reported to exert anticancer properties through the inhibition of AP-1 and NF-κB factors.


  • STAT3 (signal transducer and activator of transcription 3), is a common target for signaling pathways regulating oncogenes, as well as regulating the transduction of pro-inflammatory cytokines and growth factors. These factors contribute to the growth and survival of the cells, increasing the expression of anti-apoptotic proteins such as Bcl-2 and Bcl-xL, thereby blocking apoptosis. Several factors, such as IL-6, as well as EGFR, PDGF, leukemia inhibitory factor (LIF), oncostatin M, and the ciliary neurotrophic factor (CNTF) family of cytokines, are reported to be STAT3 activators. Besides, STAT3 is reported to be a molecular target of curcumin in many tumours, both directly and indirectly by inhibition of IL-6.

Additionally, to the mentioned transcriptional factors, pro-inflammatory cytokines—such as tumour necrosis factor alpha (TNF-α) and interleukins—have a significant role both in the inflammatory process and cancer disease. Tumour necrosis factor alpha (TNF-α) activates NF-κB, then inflammatory genes (5-LOX, COX-2), inflammatory cytokines, molecules that adhere to cells, and inducible nitric oxide synthase (iNOS) are expressed. Therefore, the transcription of TNF-α and the expression of inflammatory genes are blocked by curcumin.


The transcriptional factors NF-κB and AP-1 are also regulated by protein kinases (IκB kinases, MAPKs, and ERK1/2), hence their modification is a strategy in cancer control and prevention. There is few evidence for the ability of curcumin to inhibit protein kinases inducing apoptotic activity. Curcumin exerts its anticancer activity by acting on the level of cyclin D1 that is an important regulator of cell cycle progression and can act as a transcriptional co-regulator. The high levels of cyclin D1 has been related to the development and progression of cancer. The suppression of cyclin D1 by curcumin occurs through NF-κB inhibition. Moreover, the immunomodulatory property of curcumin is exerted not only towards molecular targets, but also cellular components such as macrophages, dendritic cells, and both T and B lymphocytes.



INTAKE:

Curcumin which is most vital component present in the turmeric has very poor bioavailability (cannot be absorbed efficient by the intestine of our body in its free form). Hence to increase its bioavailability, it is generally integrated with black pepper or vegetable oil which leads to the formation of a complex which can be easily absorbed by the intestine efficiently to have an impact on the individual and enhance the quality of life with its vital medicinal properties as listed above.


Dosage limit is also of primary importance while consuming Turmeric/Curcumin on a regular basis since its intake in a very large quantity would give rise to secondary side effects such as excessive heat and a few more complications. Thus, it can be consumed up to 2 tablespoon per day when consumed in the form of turmeric powder as food ingredient (include vegetable oil and black pepper). Turmeric powder contains around 3% curcumin, compared to 95% in case of curcumin extracts in the form of supplement. Hence 500mg capsule per day considering twice or thrice a week would be optimal dosage if consumed in the form of curcumin supplement.




GOLDEN SPICE for cancer - CURCUMIN

Turmeric also called as “THE GOLDEN SPICE”, is also termed as “Indian Saffron” due to its brilliant yellow color. The use of turmeric goes back to nearly 4000 years to Vedic culture in India, where it was used as culinary spice, for medicinal purposes and had religious significance, as its major source as curcumin. Curcumin (Diferuloylmethane) belongs to the class of polyphenols extracted from the rhizomes of Curcuma longa. This predominant natural ingredient is used worldwide for its biological properties like antioxidant, anti-inflammatory, antimicrobial, antiviral among which its anticancer potential has been the most described and remains under study till date.



Time and again, literature proves that the multiple beneficiary and medicinal properties of this curcumin (polyphenol content in turmeric) can be of great advantage to increase the wellbeing of an individual. Notably a few factors also help in preventing the further multiplication and spread of the cancer cells both in localized region as well as distant regions (in case of metastasis). These collective properties of curcumin make it a suitable option to be a vital ingredient to be included in the diet of patients undergoing treatment for various types of cancers to increase the quality of their life and can be continued during post-treatment period as well.


Curcumin has been reported to regulate transcription factors, growth factors, enzymes, kinase, inflammatory cytokines, and proapoptotic by up-regulation and anti-apoptotic by down-regulation proteins. This polyphenol compound, alone or combined with other agents could be represented one of the most effective drugs for cancer therapy.


Inflammation is a process by which body activates the immune system to protect the body from infection from outside invaders, such as bacteria and viruses. Inflammation can classified into short-lived (acute) or long-lasting (chronic). Acute inflammation goes away by few hours. Chronic inflammation can last for some months or even few years, even after the first trigger is gone.


The studies have shown that inflammation is a critical component of tumour progression. Many cancers originate from sites of infection, chronic irritation, as well as inflammation. It is understood that the tumour microenvironment is largely brought about by the inflammatory cells, is a crucial participant in the neoplastic process, fostering proliferation, survival and migration. The tumour cells have adopted some of the signaling molecules of the innate immune system, such as selectins, chemokines and their receptors for invasion, migration and metastasis (spread of cancer cells from the origin to different parts of the body).


The inflammation process brings about an increased production of pro-inflammatory molecules such as cytokines, ROS, cyclooxygenase (COX-2), transcription factors including nuclear factor κB (NF-κB), protein kinases B (AKT), activator protein 1 (AP1), signal transducer and activator of signal transducer and activator of transcription 3 (STAT3), causing the initiation and development of cancer.


Curcumin exerts its immunomodulatory ability by interacting with immune mediators (They mediate and regulate immune responses, inflammatory reactions, wound healing, hematopoiesis, and chemotaxis. Examples: Interleukins, Chemokines and lymphocytes). Hence, its anticancer property.


  • Nuclear factor κB is a pro-inflammatory transcription factor that regulate the expression of different proteins—such as cytokines interleukin-1 (IL-1), interleukin-1 (IL-2), and interferon-γ (IFNγ)—involved in multiple cell signaling pathways associated with cancer progression and inflammation. Phosphorylated NF-κB binds DNA and starts the transcription of oncogenes which block apoptosis and initiates cellular proliferation (Cell proliferation is the process by which a cell grows and divides to produce two daughter cells. Cell proliferation leads to and rapidly increase in cell number and is therefore a fast mechanism of tissue growth) and angiogenesis (Tumour angiogenesis is the growth of new blood vessels that tumours need for its further grow. The process is caused by the release of chemicals by the tumour). Curcumin suppress NF-κB activity by slowing down the phosphorylation by I kappa B kinase (IκB) and disrupt nuclear translocation of the NF-κB p65 subunit.


  • The Transcriptional factor AP-1 (Activator Protein-1) is related to anti-apoptotic (prevents apoptosis), mitogenic (provides selective growth for cells that have initiated mitosis), and pro-angiogenic genes, is downregulated by curcumin. Curcumin is reported to exert anticancer properties through the inhibition of AP-1 and NF-κB factors.


  • STAT3 (signal transducer and activator of transcription 3), is a common target for signaling pathways regulating oncogenes, as well as regulating the transduction of pro-inflammatory cytokines and growth factors. These factors contribute to the growth and survival of the cells, increasing the expression of anti-apoptotic proteins such as Bcl-2 and Bcl-xL, thereby blocking apoptosis. Several factors, such as IL-6, as well as EGFR, PDGF, leukemia inhibitory factor (LIF), oncostatin M, and the ciliary neurotrophic factor (CNTF) family of cytokines, are reported to be STAT3 activators. Besides, STAT3 is reported to be a molecular target of curcumin in many tumours, both directly and indirectly by inhibition of IL-6.

Additionally, to the mentioned transcriptional factors, pro-inflammatory cytokines—such as tumour necrosis factor alpha (TNF-α) and interleukins—have a significant role both in the inflammatory process and cancer disease. Tumour necrosis factor alpha (TNF-α) activates NF-κB, then inflammatory genes (5-LOX, COX-2), inflammatory cytokines, molecules that adhere to cells, and inducible nitric oxide synthase (iNOS) are expressed. Therefore, the transcription of TNF-α and the expression of inflammatory genes are blocked by curcumin.


The transcriptional factors NF-κB and AP-1 are also regulated by protein kinases (IκB kinases, MAPKs, and ERK1/2), hence their modification is a strategy in cancer control and prevention. There is few evidence for the ability of curcumin to inhibit protein kinases inducing apoptotic activity. Curcumin exerts its anticancer activity by acting on the level of cyclin D1 that is an important regulator of cell cycle progression and can act as a transcriptional co-regulator. The high levels of cyclin D1 has been related to the development and progression of cancer. The suppression of cyclin D1 by curcumin occurs through NF-κB inhibition. Moreover, the immunomodulatory property of curcumin is exerted not only towards molecular targets, but also cellular components such as macrophages, dendritic cells, and both T and B lymphocytes.



INTAKE:

Curcumin which is most vital component present in the turmeric has very poor bioavailability (cannot be absorbed efficient by the intestine of our body in its free form). Hence to increase its bioavailability, it is generally integrated with black pepper or vegetable oil which leads to the formation of a complex which can be easily absorbed by the intestine efficiently to have an impact on the individual and enhance the quality of life with its vital medicinal properties as listed above.


Dosage limit is also of primary importance while consuming Turmeric/Curcumin on a regular basis since its intake in a very large quantity would give rise to secondary side effects such as excessive heat and a few more complications. Thus, it can be consumed up to 2 tablespoon per day when consumed in the form of turmeric powder as food ingredient (include vegetable oil and black pepper). Turmeric powder contains around 3% curcumin, compared to 95% in case of curcumin extracts in the form of supplement. Hence 500mg capsule per day considering twice or thrice a week would be optimal dosage if consumed in the form of curcumin supplement.




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