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Effects of Turmeric Compounds on Protein Kinases Involved in Cancer

Table VI.7: Effects of Turmeric Compounds on Protein Kinases Involved in Cancer
PROTEIN KINASES AND CANCER
HOW DO THEY CONTRIBUTE TO CANCER?
AND
HOW CAN TURMERIC COMPOUNDS HELP?

Kinases are enzymes that increase the rate of production of other proteins. They do so by transferring molecules (such as phosphate) from one protein to another. Their activity (e.g., phosphorylation) serves as a signal to activate and promote other proteins important to the cell growth cycle. This includes: (vi.47, 84, 114, 118-121)

When dysregulated, kinases can help cause many diseases, including cancer. For example, pS6 kinases appear to be involved in the development and growth of a number of cancers, including squamous cell skin tumors and non-Hodgkin's lymphoma. Some uncontrolled kinases are also involved in metastasis (such as Pl3k, PAK1, and FAK) and drug resistance (e.g., thymidine). (vi.76, 81, 84, 114, 118-125)

Effect of Turmeric on Kinases

Turmeric and its curcumin compounds can both suppress and promote protein kinases. For example, curcumin downregulates mTOR and CDK4 protein kinases — both of which activate proteins that promote cancer cell growth and proliferation. (vi.5, 41-43, 126-129)

On the other hand, curcumin upregulates CHK2, a protein kinase that activates p53, a tumor suppressor. P53 stimulates production of a protein that inhibits CDK, another kinase which stops a damaged cell from progressing through the cell cycle. This gives it time to make DNA repairs. If the damage is irreparable, p53 induces the death of cancer cells. Curcumin also activates PKD1. This kinase inhibits transcription factor and structural proteins that promote prostate cancer growth and metastasis. (vi.5, 41-43, 126-128)

Curcumin's inhibition of the mammalian target of rapamycin (mTOR) kinase appears to be particularly helpful against difficult-to-treat cancers. These include head and neck cancers, malignant glioma (brain cancer), and uterine leiomyosarcoma (ULMS). (vi.13, 130)

Active Turmeric Compounds

Other compounds in turmeric that help with kinases include:
SPECIFIC EFFECTS OF TURMERIC COMPOUNDS
↓ AMPK ↑ ↓ ERK ↑ ↓ Pl3K ↓ Syk
↓ CDK1 ↓ FAK ↑ ↓ p38 MAPK ↓ Src
↓ CDK2 ↓ IκBα ↓ PKA ↓ Thymidine
↓ CDK4 ↓ IKK ↓ PKC ↓ TYK2
↓ CDK6 ↓ JAK2 ↑ PKD1  
↑ CHK1 ↑ ↓ JNK ↓ p70S6k  
↑ CHK2 ↓ mTOR ↓ pS6  
↓ EGFR tyrosine kinase ↓ PAK1    
Term often used in medical research to indicate decrease of activity. (vi.69)
Term often used in medical research to indicate increase of activity. (vi.69)
Specifically, β-catenin. (vi.127)
Cofilin. (vi.127)
Extracellular signal-regulated kinases. (vi.41)
Phosphatidylinositol 3-kinase; activates metastasis-promoting enzymes in a multiple types of cancer (e.g., breast cancer and lung cancer). (vi.76, 123)
Spleen tyrosine kinase, which promotes non-Hodgkin's B cell lymphomas. (vi.125)
Cyclin-dependent kinases that work with cyclins to regulate the cell cycle and control cell growth. (vi.81)
Focal adhesion kinases that promote invasiveness of cancer and metastasis. (vi.81)
Mitogen-activated protein kinase. (vi.41)
Promotes development of new blood vessels and invasive activity of in cancer cells. (vi.114, 121)
Activates the inflammatory transcription factor NF-κB. (vi.81)
Protein kinase A. (vi.121)
Helps activate the main inflammatory transcription factor NF-κB. (vi.56)
Protein kinase C. (vi.5)
Tyrosine kinase 2. (vi.129)
Activates STAT transcription factors. (vi.56)
Protein kinase D1, which is suppressed by prostate cancer. (vi.127)
C-Jun N-terminal kinases; activated by tumor promoters (such as UV radiation and arsenic). (vi.41, 56)
Phosphorylated S6 proteins that promote growth of skin cancer, uterine sarcoma, and head and neck cancers. (vi.7, 25, 122)
Cancer cells produce abnormally high levels of PAK1, which then overstimulates cell cycle proteins and tumor growth. (vi.114)
Tyrosine kinase 2. (vi.129)

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