Pterostilbene prevents AKT-ERK axis-mediated polymerization of surface fibronectin on suspended lung cancer cells independently of apoptosis and suppresses metastasis

doi:10.1186/s13045-017-0441-z

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Title:	Pterostilbene prevents AKT-ERK axis-mediated polymerization of surface fibronectin on suspended lung cancer cells independently of apoptosis and suppresses metastasis
Authors:	Wang, Ying-Jan Lin, Jing-Fang Cheng, Li-Hsin Chang, Wen-Tsan Kao, Ying-Hsien Chang, Ming-Min Wang, Bour-Jr Cheng, Hung-Chi
Contributors:	Natl Cheng Kung Univ, Dept Environm & Occupat Hlth Natl Cheng Kung Univ, Inst Basic Med Sci, Coll Med Natl Cheng Kung Univ, Coll Med, Dept Biochem & Mol Biol E Da Hosp, Dept Med Res Asia Univ, Dept Biomed Informat China Med Univ,China Med Univ Hosp, Dept Med Res Taipei Med Univ, Grad Inst Clin Med Natl Cheng Kung Univ Hosp, Dept Occupat & Environm Med Chia Nan Univ Pharm & Sci, Dept Cosmet Sci Chia Nan Univ Pharm & Sci, Inst Cosmet Sci
Keywords:	Fibronectin Pericellular assembly Pterostilbene Pulmonary localization PI3K/AKT/ERK signaling
Date:	2017-03-21
Issue Date:	2018-11-30 15:53:24 (UTC+8)
Publisher:	Bmc
Abstract:	Background: Polymeric fibronectin (polyFN) assembled on suspended breast cancer cells is required for metastasis. Conceivably, drugs that target such polyFN may fight against cancer metastasis. While stilbene analogs trigger proapoptotic effect on attached cancer cells, whether they prevent polyFN assembly and metastasis of suspended cancer cells via an apoptosis-independent manner remains unexplored. Methods: We depleted suspended Lewis lung carcinoma (LLC) cells of polyFN by silencing the endogenous FN expression or pterostilbene (PS) to examine whether metastasis of lung cancer cells could thus be suppressed. We investigated whether PS regulates AKT-ERK signaling axis to suppress polyFN assembly in suspended LLC cells independently of apoptosis. We tested the therapeutic effects of orally administered PS against cancer metastasis. Results: Both FN-silencing and PS among the three stilbenoids indeed significantly reduced polyFN assembly and lung metastasis of suspended LLC cells in an apoptosis-independent manner. Mechanistically, PS-induced AKT phosphorylation (pAKT) and suppressed ERK phosphorylation (pERK) in suspended LLC cells, whereas pretreatment with a PI3K inhibitor, LY294002, effectively reduced pAKT, rescued pERK, and consequently reversed the PS-suppressed polyFN assembly on LLC cells; these pretreatment effects were then overturned by the ERK inhibitor U0126. Indeed, PS-suppressed lung metastasis was counteracted by LY294002, which was further overruled with U0126. Finally, we found that PS, when orally administered in experimental metastasis assays, both significantly prevented lung colonization and metastasis of LLC cells and reduced the already established tumor growth in the mouse lungs. Conclusions: PS suppressed AKT/ERK-regulated polyFN assembly on suspended LLC cells and pulmonary metastasis. PS possesses potency in both preventing and treating lung metastasis of lung cancer cells in apoptosis-independent and apoptosis-dependent manners, respectively.
Relation:	Journal of Hematology & Oncology, v.10, pp.72
Appears in Collections:	[Dept. of Cosmetic Science and institute of cosmetic science] Periodical Articles

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