Pancreatic cancer has the highest mortality rates of all cancer types. One potential explanation for the aggressiveness of this disease is that cancer cells have been found to communicate with one another using membrane-bound vesicles known as exosomes. These exosomes carry pro-survival molecules and increase the proliferation, survival, and metastatic potential of recipient cells, suggesting that tumor-derived exosomes are powerful drivers of tumor progression. Thus, to successfully address and eradicate pancreatic cancer, it is imperative to develop therapeutic strategies that neutralize cancer cells and exosomes simultaneously. Curcumin, a turmeric root derivative, has been shown to have potent anti-cancer and anti-inflammatory effects in vitro and in vivo. Recent studies have suggested that exosomal curcumin exerts anti-inflammatory properties on recipient cells. However, curcumin’s effects on exosomal pro-tumor function have yet to be determined. We hypothesize that curcumin will alter the pro-survival role of exosomes from pancreatic cancer cells toward a pro-death role, resulting in reduced cell viability of recipient pancreatic cancer cells. The main objective of this study was to determine the functional alterations of exosomes released by pancreatic cancer cells exposed to curcumin compared to exosomes from untreated pancreatic cancer cells. We demonstrate, using an in vitro cell culture model involving pancreatic adenocarcinoma cell lines PANC-1 and MIA PaCa-2, that curcumin is incorporated into exosomes isolated from curcumin-treated pancreatic cancer cells as observed by spectral studies and fluorescence microscopy. Furthermore, curcumin is delivered to recipient pancreatic cancer cells via exosomes, promoting cytotoxicity as demonstrated by Hoffman modulation contrast microscopy as well as AlamarBlue and Trypan blue exclusion assays. Collectively, these data suggest that the efficacy of curcumin may be enhanced in pancreatic cancer cells through exosomal facilitation.

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African American men are about 1.5 times more likely to develop prostate cancer and about 2.5 times more likely to die from prostate cancer. However, there's no known cause of increased rate of morbidity and mortality in these population. Stress is well known factor for the causation of health disparities. Stress is a known inducer of post-transcriptional modification in cellular levels. Survivin, a member of the inhibitor of apoptosis family can get alternatively spliced both transcriptionally and post-transcriptionally. We have shown that survivin and its splice variants are secreted from cells via exosomes, small membrane-bound vesicles used in cell-cell and cell-extracellular communication (1,2). MicroRNAs (miRNA) are small RNA, play regulatory role in tumor development and prognosis. Main objective of the present study is to find out differential expression patterns of stress proteins and miRNA from circulating exosomes deived from prostate cancer in African American (PCa-AA) and Caucasian (PCa-CC) patient populations. This is a novel way of establishing non-invasive early detection intervention that can be tailored to Americans of different ethnicities. In this study, exosomes are collected from sera of PCa-AA and PCa-CC using the commercially available ExoQuick kit. miRNAs are extracted from the exosomes using QIAGEN miRNA kit. Differential expressions of IAPs, wild type survivin and its splice variants are noted in the exosomes of AA-prostate cancer patients' sera compared to CC-prostate cancer sera. Differentially expressed miRNAs are identified by sequencing analysis. We find that this observation will ultimately pave the way for future studies focused on analyzing these biomarkers in larger cohorts of ethnically diverse cancer patients. Citation Format: Salma Khan, TessaRae Stiff, Jennifer Simpson, James C. Lynch, Patrick Leaf, Amber Gonda, saeid mirshahidi, Tino Sanchez, Carlos A. Casiano, Nathan R. Wall. Differential expressions of stress proteins and miRNAs in circulating exosomes in prostate cancer health disparities. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B13.