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anti-cancer compounds

Dr. Bal Lokeshwar and his group are engaged in two areas of research to develop novel diagnostics and therapeutics for prostate and breast cancers. The first area is to develop targeted cancer prevention using anti-cancer compounds found in edible plant products and combining them to enhance existing systems of therapy, such as chemotherapy. In this area, the group reported anti-breast-cancer activity of compounds present in an edible spice, Pimenta dioica (Allspice). The compounds in this spice selectively killed breast cancer cells in culture dishes and slowed the growth of aggressive, metastatic breast cancer growth in animal models. Oral administration of aqueous allspice extract before the tumors are established significantly decreased tumor incidence and tumor growth. Further, the cellular basis of this antitumor activity was over-induction of autophagy but not directly apoptosis, thus demonstrating a novel mechanism of anticancer action. Interestingly, the extract did not exert any toxic effect on normal cells or non-tumor bearing mice (Oncotarget. 2015, 6(18):16379-95). The atypical CXC-chemokine receptor CXCR7 is a 7-transmembrane receptor that is over-expressed in estrogen-receptor-positive breast cancer cells, where it functions independently of its chemokine ligand CXCL-12 (SDF-1). The mechanism behind this observation was shown to be a consequence of the CXCR7 regulation of breast cancer cell survival and proliferation by enhancing epidermal growth factor (EGF)-induced stimulation of cancer cell growth and motility, a mechanism that is hormone (17-β estradiol)-independent in early-stage breast cancer tissues and established ER-positive breast cancer cells. This research showed co-localization of the EGF-Receptor (EGFR) and CXCR7, and migration to the nucleus to enhance cell proliferation. Depletion of CXCR7 in breast cancer cells reduced clonogenic growth of tumor cells and decreased tumor cell motility (Mol Cancer. 2014, 13:198). Ongoing studies also show that the CXCR7-EGFR interaction is regulated by the scaffold protein β-Arrestin 2. Dr. Bal Lokeshwar also participated in an international effort to bring together cancer experts engaged in exploring a multi-targeted approach to suppress tumor-promoting inflammation and in identifying natural products that exploit these targets to destroy tumors. This multi-national project has produced and reported its findings in a thematic issue of Seminars in Ca