BERKELEY, CA (UroToday.com) - Prostate cancer is the second leading cause of cancer death and the most commonly diagnosed cancer in the US. The early stages of prostate cancer are highly amenable to medical intervention.[1]
Unfortunately in most cases, however, the tumor progresses to androgen-independent stage for which no effective therapy is currently available.[1, 2] Aging is a primary risk factor for prostate cancer development. Consequently, as human longevity increases, prostate cancer will become a bigger challenge for our times and the future.[2] Therefore, it is highly desirable to understand the molecular basis of the disease and capitalize on this information to develop newer strategies for prevention and improvement of conventional chemotherapeutic treatment of prostate cancer.
Epidemiological studies indicate a potential link between specific diet and cancer prevention.[1] The role of diet in the development of prostate cancer has received particular interest for many years due to lower incidences of prostate cancer in east-Asian countries compared to the western world.[1] Western diets are rich in processed foods that are high in calories and low in nutritional values. This differs significantly from eastern diets which are primarily plant based and are high on unprocessed food items like fruits and vegetables. Therefore, components of eastern diet, like curcumin, have been the focus of study as a means to prevent or delay prostate cancer development and progression.[3, 4]
Curcumin, is a non-toxic, diferuloyl methane compound that forms the active ingredient of the natural compound turmeric.[4] While turmeric is a commonly used spice in Indian cuisine, it has also been traditionally used in Indian and Chinese medicine for the treatment of various ailments, including inflammation and wound healing. Recent stringent scientific experiments have also established the ability of curcumin to effectively inhibit cancer growth.[4, 5] Curcumin’s anti-cancer effect is directly related to its ability to simultaneously modulate the functions of many cell-signaling pathways, including the nuclear β-catenin/T cell Factor 4 (TCF4) signaling pathway, which is mutated in multiple cancers.[4, 5] Therefore, regulating the nuclear β-catenin signaling pathway using drugs, or by modulating the functions of its protein regulators, will greatly aid in devising newer strategies for the treatment of prostate cancer.[6]
We have discovered a novel molecular mechanism by which curcumin inhibits prostate cancer growth.[7] Using cell culture and animal models of prostate cancer we have demonstrated, for the first time, that curcumin activates the protein kinase D1 (PKD1) molecule resulting in the suppression of β-catenin signaling activity. This decrease of nuclear β-catenin function correlates with a decrease in cell proliferation, colony formation and cell motility, and enhanced cell-cell aggregation in prostate cancer cells. The discovery of this novel pathway is significant since PKD1 appears to suppress prostate cancer. Previous work from our laboratory has shown that PKD1 is decreased in prostate cancer, and the reduction in PKD1 levels/functions is directly proportional to the severity of the cancer.[8]
An extrapolation of this novel observation is the implication of curcumin use in the prevention of prostate cancer development. It is plausible that regular consumption of curcumin regulates the levels or activity of PKD1 to prevent the development of prostate cancer. While further studies and clinical trials are clearly needed to establish this aspect, our paper demonstrates a novel mechanism through which curcumin exerts its anti-cancer effect and may prevent prostate cancer development.
Figure 1. Turmeric powder. Curcumin is the active ingredient of turmeric
Figure 2. Structure of Protein Kinase D1 (PKD1)
References:
- Denmeade SR, Isaacs JT (2002) A history of prostate cancer treatment. Nat Rev Cancer: 389-396.
- Feldman BJ, Feldman D (2001) The development of androgen-independent prostate cancer. Nat Rev Cancer 34-45.
- Mukhopadhyay A, Bueso-Ramos C, Chatterjee D, Pantazis P, Aggarwal BB (2001) Curcumin downregulates cell survival mechanisms in human prostate cancer cell lines. Oncogene 7597-7609.
- Sundram V, Chauhan, SC, Kumar, D and Jaggi, M (2012) Signaling pathways modulated by curcumin in cervical cancer. Current advances in Gynecological Oncology Chauhan SC BMJM, editor.
- Kunnumakkara AB, Anand P, Aggarwal BB (2008) Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins. Cancer Lett 269 199-225.
- Jaggi M, Chauhan SC, Du C, Balaji KC (2008) Bryostatin 1 modulates beta-catenin subcellular localization and transcription activity through protein kinase D1 activation. Mol Cancer Ther 2703-2712.
- Sundram V, Chauhan SC, Ebeling M, Jaggi M (2012) Curcumin Attenuates beta-catenin Signaling in Prostate Cancer Cells through Activation of Protein Kinase D1. PLoS One 7(4): e35368.
- Jaggi M, Rao PS, Smith DJ, Hemstreet GP, Balaji KC (2003) Protein kinase C mu is down-regulated in androgen-independent prostate cancer. Biochem Biophys Res Commun 254-260.
Written by:
Vasudha Sundram,a Subhash C. Chauhan,a, b Mara Ebeling,a and Meena Jaggia, b as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
aCancer Biology Research Center, Sanford Research/USD, Sioux Falls, South Dakota USA
bDepartment of OB/GYN and Basic Biomedical Science Division, Sanford School of Medicine, The University of South Dakota, Sioux Falls, South Dakota USA
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