Curcumin Investigated to Prevent Prostate Cancer Metastasis
NCI CAM Annual Report-FY10Prostate cancer claims the lives of about 30,000 men each year in the United States. Those deaths are due almost entirely to metastasis, or spread of the cancer to other organs. Approximately 75% of men with early-stage prostate cancer can be successfully treated with surgery and will not have a recurrence of their disease. Oncologists, however, currently lack the ability to accurately distinguish the remaining 25% of patients at high risk for recurrence who would benefit from adjuvant, or additional, therapy after surgery.”
A recent study* identified a trio of substances known as chemokines (small proteins secreted by cells) found in prostate tissue that accurately predicted whether prostate cancer would recur within five years of surgery. When prostate tissue contained abnormally high amounts of two of these substances, known as CX3CL1 and IL-15, the cancer was highly unlikely to recur within that period. By contrast, when tissue contained abnormally high amounts of the third identified chemokine, CCL4, recurrence was likely.
Magaly Martinez-Ferrer, Ph.D., of the University of Puerto Rico Comprehensive Cancer Center (UPRCCC) – one of the researchers who participated in the study – is now trying to extend these findings by determining whether this trio of chemokines can affect prostate cancer metastasis. In addition, with NCI funding in the form of a Continuing Umbrella of Research Experience (CURE) K01 diversity training grant**, she is examining whether treatment with curcumin, a chemical component of the spice turmeric, can promote or inhibit metastasis by modifying the levels of these chemokines in prostate tissue.
Curcumin has previously been shown to inhibit colon tumors and, in some studies, has been associated with a reduction in the size of prostate tumors, according to Dr. Martinez-Ferrer. Other studies have found that curcumin has anti-inflammatory properties, although the mechanism for this is unclear. Previous research also suggests that chronic inflammation may promote prostate cancer metastasis. A randomized, double-blind, placebo-controlled clinical trial is currently under way at UPRCCC to determine whether curcumin can shrink precancerous growths in patients with a genetic disorder that puts them at an extremely high risk for colorectal cancer.
At the 2011 American Association for Cancer Research annual scientific meeting, Dr. Martinez-Ferrer reported the initial results of experiments in which CX3CL1 and IL-15 chemokines were added to a highly metastatic prostate cancer cell line.*** The addition of the chemokines significantly decreased proliferation and migration of the cells, suggesting that they may suppress metastasis.
Dr. Martinez-Ferrer plans to investigate whether treatment with curcumin modifies metastasis, tumor size, or inflammation in both cell lines to which CX3CL1 and IL-15, or CCL4 have been added, or in laboratory mice implanted with prostate tumors.
She hopes this work will ultimately show that these three chemokines can either promote or inhibit prostate cancer metastasis and, further, that treatment with curcumin can modify these effects by altering levels of these chemokines in prostate cancer cells or in laboratory mice. If that proves to be the case, the next step, according to Dr. Martinez-Ferrer, would be to conduct a clinical trial in which patients at risk for prostate cancer recurrence would be treated with curcumin to determine whether this intervention reduces the risk of disease metastasis.
*Blum DL, Koyuama T, M’Koma AE, et al. Chemokine markers predict biochemical recurrence of prostate cancer following prostatectomy. Clinical Cancer Research, 2008; 14(23): 7790-7
**Grant number: 7K01CA140711-02
***Martinez-Ferrer M, Qi Y, Sanchez MM, Bhowmick NA. Inflammatory mediators of prostate cancer metastasis. Abstract #391, presented at American Association for Cancer Research 102nd Annual Meeting; April 3, 2011; Orlando, FL.