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Bioactive compounds to prevent galectin‐mediated metastasis of prostate cancer
Author(s) -
Guha Prasun,
Kaptan Engin,
Vasta Gerardo R.,
Ahmed Hafiz
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.557.1
Subject(s) - apoptosis , cancer research , metastasis , chemistry , cancer cell , cell adhesion , galectin 3 , immune system , cell , microbiology and biotechnology , biology , cancer , immunology , biochemistry , genetics
Although many chemotherapeutic drugs are initially beneficial, most tumors including prostate cancer (PCa) become drug resistant and metastasize. Galectin‐3 (gal3), a beta‐galactoside‐binding lectin may be involved in attenuating drug response. Intracellular gal3 enhances mitochondrial stability and inhibits apoptosis in PCa cells induced by chemotherapeutics. Extracellular gal3 promotes tumor cell adhesion as well as tumor‐endothelial cell adhesion through interactions of cancer cells‐associated Thomsen‐Friedenreich disaccharide (TFD) with endothelium‐expressed gal3. Moreover, tumor‐secreted gal3 induces apoptosis of infiltrating T cells, thus acting as double‐edged sword to evade immune surveillance during tumor progression. We hypothesize that exogenous TFD would block gal3‐mediated homotypic aggregation and tumor cell‐endothelial interactions to prevent metastasis. Further, these carbohydrates would also block gal3 mediated T‐ cell apoptosis, to facilitate anti‐tumor immune response. For this purpose, we have partially purified TFD containing glycopeptide from marine fish that is 22‐fold better than the synthetic TFD in inhibiting gal3‐binding. The TFD containing glycopeptide inhibited tumor cell adhesion to endothelial cells and also blocked gal3 mediated apoptosis T cells. [Supported by grants USAMRMC W81XWH‐07‐1‐0565 and NIH RO3CA133935‐01, R41CA141970‐01 to HA]