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DHA Supplementation Alters Cofilin1/pVASP‐S239 Expression, Sub‐cellular, Localization, and Suppresses Migration and Proliferation in Lung Cancer Cells
Author(s) -
Ali Mehboob,
Heyob Kathryn M,
Rogers Lynette K
Publication year - 2016
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.30.1_supplement.688.5
Subject(s) - cell migration , cancer cell , microbiology and biotechnology , cell growth , metastasis , actin cytoskeleton , cell , biology , cancer , chemistry , cancer research , cytoskeleton , biochemistry , genetics
Cancer cells exhibit higher migration rates and greater cell viability facilitated by actin binding protein (ABP)‐mediated cytoskeletal remodeling and secondary messengers. APB like vasodilator stimulated phosphoprotein (VASP) and cofilin1 regulate actin remodeling. cGMP mediated VASP phosphorylation at serine 239 (pVASP‐S239) via PKG and cofilin1 are associated with actin stabilization. Docosahexaenoic acid (DHA) has been shown inhibit cancer cell metastatic phenotype. We hypothesize that DHA enhances pVASP‐S239 and its association with cofilin1 to attenuate actin dynamics‐mediated cancer cell migration and survival. Non‐cancer (MLE12) and cancer (A549) cells were treated with DHA for 6h and 24h. pVASP‐S239 and cofilin1 expression were analyzed by western blot and total F‐actin content and VASP/cofilin expression and localization were assessed by immunofluoresence. Cell migration was estimated by wound assay and transwell apparatus. Ki67 and caspase 3 expressions measured by flow cytometry. Protein expression of pVASP‐S239 and cofilin1 increased with DHA supplementation compared to control. F‐actin content, cell migration, and proliferation were decreased with DHA supplementation in cancer cells but not in non‐cancer cells. With stimulation, cellular distribution of cofilin1 and pVASP‐S239 were observed in the perinuclear region while DHA supplementation caused the expression to moved towards cellular edges. In conclusion, DHA specifically inhibits cancer cell migration and proliferation and this effect correlates with ABP expression and subcellular distribution patterns. DHA supplementation suppresses cellular changes related to metastatic potential in cancer cells and could provide therapeutic potential against cancer cell metastasis. Support or Funding Information This work was supported by the National Institutes of Health, NCCIH/ODS (LKR R01AT006880).