ABSTRACT: Prostate cancer has high incidence and mortality rates, especially in Hispanics and African Americans when compared with White Americans. Most men with advanced disease eventually stop responding to traditional androgen-deprivation therapy, suspected to be due to enhancement of autocrine and/or paracrine androgen synthesis within the tumor microenvironment. Although some therapeutic agents have demonstrated efficacy in the metastatic setting, it has been at great cost and significant side effects. There is still a need to explore therapeutic alternatives that are well-tolerated, have few side effects and minimal cost. Exploring novel compounds that have been attributed anti-tumor and immunomodulatory capabilities can be proven capable of modifying the tumor microenvironment and overcoming the tumor-induced immunosuppressive state.
Curcumin, a natural compound derived from the plant Curcuma longa, has previously been shown to possess anticancer properties through modulating multiple molecular targets related to apoptotic pathways in tumors. Other “in vitro” as well as “in vivo” studies have also provided important insights of curcumin as an immunomodulator by inhibiting inflammation and mediating the activation and function of immune cells, especially cytotoxic CD8+ T cells and NK cells. Although the connection of curcumin and immunoenhancement is evident, further investigations are needed in humans with cancer. If anti-tumor activity is demonstrated, curcumin has potential for future clinical immunotherapeutic applications. In this proposed study, curcumin will be evaluated as immunomodulator.
Central Hypothesis: Curcumin will activate lymphocytes from metastatic prostate cancer patients and induce its anti-tumor activity.
Objectives: To test our hypothesis the following specific aims will be proposed: Specific Aim 1: To evaluate the cell-mediated cytotoxicity activity of curcumin-activated lymphocytes obtained from 20 patients with metastatic prostate cancer. Specific Aim 2: To analyze the percentage distribution of prostate cancer patients’ lymphocytes secreting perforin and granzyme B following curcumin treatment. Specific Aim 3: To measure pro- and anti-tumor cytokine production of prostate cancer patients’ lymphocytes treated with curcumin.
Significance: This proposed pilot study will provide sufficient information on the “in vitro” immunomodulatory effect of curcumin in lymphocytes obtained from metastatic prostate cancer patients whose immune system are mostly suppressed by oncologic treatment. This study will open the possibility of activating lymphocytes with curcumin in the cancer patient. Based on these results, it will provide the basis for the development new immunotherapeutic strategies for future clinical studies.