Metastasis of breast tumor cells to brain is suppressed by targeting RLIP alone and in combination with 2′-Hydroxyflavanone. (1st December 2018)

• Record Type: Journal Article
• Authors: Singhal, Jyotsana; Singhal, Preeti; Horne, David; Salgia, Ravi; Awasthi, Sanjay; Singhal, Sharad S.
• Is Part Of: Cancer letters. Volume 438(2018)
• Page Start: 144
• Page End: 153
• Publication Date: 2018-12-01
• Subjects: RLIP -- Breast cancer -- Phytochemicals -- Brain metastasis -- Chemotherapeutics; BC breast cancer -- EMT epithelial-mesenchymal transition -- ER estrogen receptor -- GSH glutathione -- GS-E glutathione-electrophile conjugate -- 2HF 2′-hydroxyflavanone -- Luc luciferase -- NSG NOD scid gamma -- PIS pre-immune serum -- PR progesterone receptor -- TNBC triple negative breast cancer -- Rab RLIP-antibody -- RLIP a 76 kDa ral-interacting protein -- siRNA small interfering RNA -- STR short tandem repeat; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2018.09.015
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: Brain metastasis is an important cause of morbidity and mortality in cancer-patients. Breast tumor cells frequently metastasize to brain and initiate severe therapeutic complications. In the present study, we evaluated the anti-metastatic effects of 2′-hydroxyflavanone (2HF) alone and in combination with RLIP targeted therapy in a novel murine model of breast tumor metastasis. The MDA-MB231Br (brain-seeking) breast cancer (BC) cells stably-transfected with luciferase were injected into the left-ventricle of NSG mouse heart and the migration of cells to brain was monitored using a non-invasive bioluminescent imaging system. To evaluate the tumor growth suppressive effects, mice were given 2HF (50 mg/kg, b.w., alternate days orally), RLIP-antibody (Rab; 5 mg/kg, b.w., weekly i.p. ) or combination of 2HF+Rab starting day1 after intra-cardiac injection. Our results reveal that 2HF and Rab significantly prevented the metastasis of BC cells to brain. Further, mice treated with combination of 2HF+Rab exhibited no metastasis as compared to either or the single agent-treated mice. This study for the first time demonstrates the anti-metastatic effects of 2HF and RLIP-inhibition in-vivo in a novel breast tumor metastasis model and provides the rationale for further clinical investigation. Highlights: Anti-metastatic potential of 2HF. RLIP, a potential molecular target in breast cancer (BC). 2HF exerts its anticancer effects by targeting and/or inhibiting RLIP. 2HF inhibits pERK, pSTAT3, and pAKT expression. 2HF inhibits RLIP and significantly prevented the metastasis of BC cells to brain.