Cancer, TGF-β and curcumin
Cytokines are signalling molecules that orchestrate immune system activity, among which TGF-β (Transforming Growth Factor-Beta) is being recognized by numerous studies to have an important role in the immune response to cancers.
The authors of a paper just now being published in the European Journal of Cancer note the dual activity of TGF-β, and acknowledge that related treatments are being pursued:
"Transforming growth factor (TGF)-β signalling plays a dichotomous role in tumour progression, acting as a tumour suppressor early and as a pro-metastatic pathway in late-stages. There is accumulating evidence that advanced-stage tumours produce excessive levels of TGF-β, which acts to promote tumour growth... In light of the pro-metastasis function, many strategies are currently being explored to antagonise the TGF-β pathway as a treatment for metastatic cancers."
A similar paper published in the journal Expert Opinion on Investigational Drugs also states:
"The transforming growth factor-ß (TGF-β) signaling pathway plays a pivotal role in diverse cellular processes. TGF-β switches its role from a tumor suppressor in normal or dysplastic cells to a tumor promoter in advanced cancers."
They too note the enthusiasm for TGF-β inhibition in developed malignancies:
"TGF-β signaling has been considered a useful therapeutic target. The discovery of oncogenic actions of TGF-β has generated a great deal of enthusiasm for developing TGF-β signaling inhibitors for the treatment of cancer."
A review published a month later in Expert Opinion on Therapeutic Targets considers inhibition of TGF-β specifically for prostate cancer:
"TGF-β regulates prostate growth by inhibiting epithelial cell proliferation and inducing apoptosis through eliciting a dynamic signaling pathway. In metastatic prostate cancer, however, TGF-β serves as a tumor promoter."
They define very nicely the need to take a balanced approach in consideration of the dual role of TGF-β:
""The molecular basis for effective therapeutic targeting of TGF-β must be directed towards the double-edge-sword nature of the cytokine: Inhibiting the TGF-β tumor promoter capabilities in advanced metastatic prostate cancer, although retaining the growth-inhibitory abilities exhibited in early stages of prostate tumorigenesis."
Now consider this fascinating research just now being published in the journal Cellular & Molecular Immunology on the ability of curcumin (an extract of turmeric) to reduce the undesirable action of TGF-β. The authors begin by observing:
"Immune dysfunction is well documented during tumor progression and likely contributes to tumor immune evasion...Tumors often target and inhibit T-cell function to escape from immune surveillance. This dysfunction includes loss of effector and memory T cells, bias towards type 2 cytokines and expansion of T regulatory (Treg) cells."
Interestingly, not only did curcumin prevent the loss of T cells and reverse the type 2 immune bias...
"Further investigation revealed that tumor burden upregulated Treg cell populations and stimulated the production of the immunosuppressive cytokines transforming growth factor (TGF)-β and IL-10 in these cells. Curcumin, however, inhibited the suppressive activity of Treg cells by downregulating the production of TGF-β and IL-10 in these cells...curcumin treatment enhanced the ability of effector T cells to kill cancer cells. Overall, our observations suggest that the unique properties of curcumin may be exploited for successful attenuation of tumor-induced suppression of cell-mediated immune responses."
You may also wish to read an earlier post on cytokines and prostate cancer. I hope this makes it clear why I consider the measurement of TGF-β an important laboratory test for my patients in these circumstances, and curcumin a potentially valuable therapeutic ally. Be sure to discuss these with your doctor if the need arises.