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Expression of platelet‐activating factor‐receptor potentiates the cytotoxicity of benzyl isothiocyanate in melanoma cells (LB332)
Author(s) -
Sahu Ravi
Publication year - 2014
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.28.1_supplement.lb332
Subject(s) - melanoma , cancer research , benzyl isothiocyanate , apoptosis , cell growth , platelet activating factor , fluorescein isothiocyanate , chemistry , medicine , pharmacology , isothiocyanate , immunology , biochemistry , physics , quantum mechanics , fluorescence
Malignant melanoma is currently the most rapidly growing malignancy with >11,000 estimated annual mortality in the United States. Because melanoma is resistant to chemo and radiotherapies, investigation of novel therapeutic target(s) and approaches are required. Platelet‐activating factor‐receptor (PAF‐R) plays crucial roles in regulating cancer growth. Benzyl isothiocyanate (BITC), present in cruciferous vegetables possess anticarcinogenic properties against various cancers. Since, most elanomas express PAF‐Rs, the present studies investigated efficacy of BITC against melanoma cells expressing or non‐expressing PAF‐R. Studies using novel model systems consisting of murine B16F10 melanoma cells ectopically expressing PAF‐R (B16‐PAFR) or vector control (B16‐MSCV) created by retroviral mediated transduction, demonstrate that BITC dose‐dependently decrease the survival of B16‐PAFR cells substantially compared to B16‐MSCV cells. In contrast, PAF‐R agonist, CPAF induced enhance proliferation of only, B16‐PAFR cells, indicating the importance of PAF‐R in melanoma progression. To determine the mechanism, BITC‐treatments resulted significantly increased reactive oxygen species (ROS) generation in B16‐PAFR cells compared to B16‐MSCV cells, and was blocked by vitamin C. In addition, BITC induced increase apoptosis in B16‐PAFR cells. Importantly, BITC‐induced increase cell death, ROS and apoptosis in B16‐PAFR cells were blocked by vitamin C and PAF‐R antagonist. Moreover, BITC significantly suppressed the growth of B16‐PAFR melanoma xenografts in NOD‐SCID mice via inducing apoptosis. Finally, BITC significantly decreased the survival of PAF‐R positive human melanoma cells compared to PAF‐R negative cells. These studies indicate that BITC could be used as a novel chemopreventive agent against PAF‐R expressing melanoma cells.Grant Funding Source : AICR 09A062, ACSIRG 4185607, Showalter Research Trust Fund 4485602