Colorectal cancer (CRC) is a frequently diagnosed cancer and causing significant mortality in the patients. Metastasis caused by CRC is mainly responsible for this cancer-related deaths. Despite recent advancements in the treatment methods, prognosis remains poor. Therefore, effective treatment strategies need to be designed for successful management of this disease. Dehydroepiandrostenedione (DHEA), a 17-ketosteroid hormone produced by adrenal glands, gonads and including gastrointestinal tract is required for several physiological processes. Deregulation of DHEA levels leads to various disease conditions including cancer. In fact, several experimental studies strongly suggest that DHEA could be used as a chemopreventive agent against colon cancer. Prenlyation of certain membrane proteins such as phosphatase of regenerating liver-3 (PRL-3) is crucial for metastatic progression of colon cancer cells. The ability of DHEA to target prenylation pathway could be utilized to inhibit PRL-3 prenylation for successful prevention of CRC metastases. As DHEA is a widely consumed drug for various ailments, incorporation of DHEA in the treatment regimen may be beneficial to prevent or delay the occurrence of metastasis resulting from CRC.

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Membrane lipid peroxidation and DNA, protein damage is mediated by free radicals, which form the basis of chronic pathological complications.AgNPs are an important class of nanomaterials for a wide range of biomedical applications. The present study endeavors in vitro antioxidant and anti-inflammatory activity of green synthesized silver nanoparticles (AgNPs) using medicinal plant extract from Caesalpinia bonducella seeds. Total flavonoid and phenolic contents were determined. The antioxidant potential of capped AgNPs was assessed using DPPH assay, Phosphomolybdenum assay, FRAP assay, metal chelating, hydrogen peroxide, and hydroxyl radical scavenging methods. In vitro anti-inflammatory assay of CB seed, AgNPs were performed against the standard drug. CB seed AgNPs possessed high flavonoid and phenol compared to aqueous CB seed extract. The antioxidant methods confirmed that the silver nanoparticles have more antioxidant activity as compared to vitamin C. The synthesized silver nanoparticles exhibited potential anti-inflammatory activity with the IC50 71.3µg/ml. Hence, this work clearly demonstrated that the coated AgNPs with CB seeds act as a potent free radical scavenger and could be considered as a potential source for anti-inflammatory drugs.

Prostate carcinoma (PCa) is one of the most frequently diagnosed cancers in US men causing an estimated 30,000 deaths annually. The primary cause for deaths related to PCa is the development of metastases. Although these patients initially respond to traditional androgen ablation therapy, they invariably develop metastasis and shortened life span following treatment failure. What causes metastases in PCa patients remains poorly understood. Recently, Phosphatase of Regenerating Liver-3 (PRL-3) has been discovered as a unique gene involved in the promotion of metastasis of several cancers including colorectal cancer, ovarian cancer, breast cancer, cervical cancer, and lung cancer. However, its involvement in PCa metastases is not yet known. Our current studies utilizing chromosomal microarray analysis confirmed that PRL-3 gene is amplified in prostate cancer. Additional studies conducted using real-time PCR and Western blot analyses confirmed that PRL-3 is overexpressed in advanced prostate cancer cells. To determine the functional significance of PRL-3 expression in PCa pathology, we designed a series of studies (cell proliferation, anchorage-independent growth, and migration assays as endpoints) to therapeutically target PRL-3 expression using DU145 and PC-3 metastatic cell lines as model systems. Targeting PRL-3 expression either by RNAi or by pharmacological inhibition using 5-[[5-bromo-2-[(2-bromophenyl)methoxy]phenyl]methylene]-2-thioxo-4-thiazolidinone resulted in substantial reduction of PCa cell proliferation, anchorage-independent growth and migration ability of these PCa cells. Furthermore, we identified dibenzoyl methane (DBM), a curcumin analog present in licorice root, as a potential non-toxic natural inhibitor of PRL-3 in PCa cells. Specifically, DBM treatment downregulated the expression of PRL-3 resulting in the inhibition of cell proliferation, loss of anchorage-independent growth and mitigating the motility of PC-3 and DU145 cells in vitro. Importantly, administration of DBM to nude mice bearing prostate tumors derived from PC-3 and DU145 cells resulted in regression of these tumors. To gain further mechanistic insights into how PRL-3 expression promotes aggressive traits in PCa cells, cell signaling studies were carried out using panel of PCa cell lines. These studies revealed that Translationally Controlled Tumor Protein and dsRNA dependent protein kinase R may be important mediators of PRL-3 aggressive behavior in PCa cells. Our results for the first time show that PRL-3 may have a prominent role in the progression of PCa and may serve as a potential prognostic and therapeutic target for advanced PCa. Citation Format: Jyotsna Sundar, Joseph Devito, Michael Tyrkus, Maarten C. Bosland, André Kajdacsy-Balla, Gnanasekar Munirathinam. Phosphatase of regenerating liver-3 (PRL-3): a novel metastatic taret for prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4381. doi:10.1158/1538-7445.AM2013-4381