DNA Transcription Factors

Effects of Turmeric Compounds on Transcription Factors, Co-Factors, and Oncogenes Involved in Cancer

Table VI.1: Effects of Turmeric Compounds on Transcription Factors, Co-Factors, and Oncogenes Involved in Cancer
How do they contribute to cancer?
How can turmeric compounds help?

Turmeric's Activity Depends on Type of Transcription Factor

The turmeric compound curcumin and its analogues block a number of different transcription factors that activate oncogenes. These genes are involved in the development of cancer (carcinogenesis), tumor growth, and metastasis(vi.25713343941-4347-56)

On the other hand, curcumin stimulates beneficial transcription factors. For example, some of these prompt genes to produce natural detoxifying antioxidants and enzymes. By quenching free radicals and getting rid of toxins, they help prevent cancer and stop malignant cells from replicating. (vi.25713343941-4347-5557)

Variations of Some Transcription Factors Can Act in Opposite Ways in Cancer

Curcumin increases activation of the transcription factor PPAR-γ and PPAR-α. Both of these transcription factors help control cell growth. PPAR-γ also helps regulate inflammatory and immune system responses in cells. When activated in the presence of cancer cells, PPAR-γ suppresses tumor growth and metastasis. It does so by: (vi.394258-62)

Conversely, PPAR-δ prevents cancer cells from dying. High levels of PPAR-δ are found in several different types of cancer, such as: (vi.44258-5963-65)

Lab studies show curcumin suppresses PPAR-δ in cancer cells. (vi.44258-5963-65)

Curcumin's Effects are Cancer-Dependent

Studies show that the way turmeric's curcumin compounds regulate transcription factors depends on the type of cancer they encounter. In fact, curcumin sometimes stimulates a transcription factor in one cancer but blocks the same factor in a different type of cancer. Medical researchers suggest that these seemingly contradictory effects could actually be an indication of curcumin's ability to adjust its behavior depending upon the type of cancer involved. (vi.66)

For example, in lab tests curcumin blocks the growth of colon cancer by suppressing Egr-1, which inhibits the epidermal growth factor (EGF) and its receptor (EGFR) proteins. But it activates Egr-1 to stimulate production of tumor suppressors that block glioblastoma type of brain tumor cells from growing. (vi.66)

AHR — Detoxifying or Carcinogenic Transcription Factor?

Interestingly, aryl hydrocarbon receptor (AHR) is another transcription factor that turmeric's curcumin compounds help regulate. Certain toxic chemicals linked to cancer bind to and activate AHR, which then triggers genes to make phase I and II metabolizing enzymes. These enzymes break down the toxins and lead to cancerous activity in cells. Higher levels of both AHR and phase enzymes are associated with more aggressive cancer cell lines. (vi.67)

Curcumin compounds in turmeric also activate AHR and lead to higher levels of liver enzymes. However, studies suggest that when it's activated by natural compounds such as curcumin, AHR may actually help prevent cancerous activity. How does this happen? One study involving head and neck cancer cells exposed to tobacco toxins and treated with curcumin may explain the difference. Even though the turmeric compound activated AHR and increased phase enzyme levels, it prevented the enzymes from breaking down the tobacco toxins into the more carcinogenic metabolites. (vi.67)

Curcumin also activates AHR in leukemia cells and induces cancer cell death. However, studies have determined that while curcumin promoted apoptotic death in leukemia cells, binding to AHR was not the primary reason for its cancer-suppressing effects. (vi.68)

Curcumin Curtails the Activity of Cofactors

Studies indicate that curcumin helps regulate expression of some cofactors that activate transcription factors involved in cancer development and progression. For example, curcumin can inhibit expression of the androgen receptor transcription factor (AR), involved in prostate cancer, by blocking AR's cofactors. (vi.53969-70)

Other Active Turmeric Compounds

Other compounds in turmeric known to have beneficial effects on transcription factors involved in cancer include:

Akt c-jun MDM2 Skp2
AP-1 c-myc MITF Sp-1, Sp-2, Sp-3
β-catenin E2F-1 PPAR-α STAT4
BTG2 E2F-5 PPAR-γ STAT5a & b5
CBP Egr-1 PPAR-δ Wilms' tumor gene 1
CHOP EIF4E p300  
Curcumin compounds (e.g., CDF) that have been modified to increase how long it stays available in the body before being broken down. (vi.53)
For example, Notch-1, EGFR, c-jun, and c-myc. (vi.25343941-4247-48)
For example, phase II enzymes in the liver and other antioxidant proteins, such as HO-1, GST, NAD(P)H, and GI-GPx. (vi.25343941-4247-48)
Peroxisome proliferator-activated receptor-gamma. (vi.39)
Cancer in the bile ducts. (vi.4)
Hepatocellular carcinoma. (vi.4)
Such as p21. (vi.66)
Also known as protein kinase B (PKB); helps cancer cells survive by inhibiting proteins that get rid of damaged cells. (vi.50)
An oncogene important to tumor development and growth. (vi.43)
Activator protein-1 promotes cancer development, growth, and metastasis; it controls growth factors such as VEGF that help supply blood to tumors. (vi.3947)
Helps control growth of normal and malignant cells; if deregulated, it promotes growth and metastasis in solid tumors, lymphoma, and leukemia. (vi.39)
Activates gene responsible for production of melanin pigments in the skin. Too much MITF promotes skin cancer. (vi.54)
Promotes various cancers (e.g., breast, colon, and lung cancer) and protects damaged cells from tumor suppressors. (vi.65)
Acronym for ataxia telangiectasia mutated, a gene that produces kinase proteins that work to repair or get rid of cells with damaged DNA before they can turn cancerous. (vi.51)
CREB produces beneficial neuron growth factors in the brain, but in can promote prostate cancer. Curcumin promotes CREB in the brain but suppresses it in prostate cancer cells. (vi.43)
Promotes growth of head and neck cancers, multiple myeloma, leukemia, lymphoma, and some solid tumors. (vi.5665)
Promotes cell cycle proteins that help tumor cells grow and replicate (such as in breast and colon cancers). (vi.2)
Helps block cancer growth by inhibiting cell growth cycle proteins (such as cyclin D1). (vi.42)
Promotes tumor growth by stimulating the replication of cancer cells when deregulated. (vi.42)
Increases expression of growth factors and proteins that block cancer cell death (as does STAT3). (vi.56)
CREB-binding protein; CBP is a cofactor for the androgen receptor transcription factor and could help against prostate cancer. (vi.39)
Stimulates production of growth factor receptors and cell cycle proteins that promote tumors and new blood vessels they need to grow. (vi.3947)
C/EBP homologous protein. (vi.57)
Promotes growth of head and neck cancers. (vi.13)
Small proteins produced as part of the immune system response to illness or injury. (vi.3787)
Holding cells together and helping them communicate (vi.4789117)

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