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AIM To develop a leptin peptide receptor antagonist linked to nanoparticles and determine its effect on viability of breast cancer cells.METHODS The leptin antagonist, LPrA2, was coupled via EDAC [1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide] to iron oxide nanoparticles(IONP-LPrA2) to increase its efficacy.IONP-LPrA2 conjugation was confirmed by Western blot and nanoparticle tracking analysis.Human triple negative breast cancer(TNBC) MDA-MB-231, HCC1806 and estrogen receptor positive(ER+) MCF-7 cells were analyzed for the expression of the leptin receptor, Ob-R.The effects of leptin and antagonist on levels of leptin-induced STAT3 phosphorylation and cyclin D1, cell cycle progression, cell proliferation, and tumorsphere formation in breast cancer cells were determined.Doses of the chemotherapeutics [cisplatin(Cis), cyclophosphamide(CTX), doxorubicin(Dox) and paclitaxel(PTX)] to effectively reduce cell viability were calculated.The effects of combination treatments of IONP-LPrA2 and chemotherapeutics on cell viability were determined.RESULTS Western blot analysis of coupling reaction products identified IONP-LPrA2 at approximately 100 kD.IONPLPrA2 significantly decreased leptin-induced p STAT3 levels in HCC1806 cells and drastically decreased cyclin D1 levels in all cell lines.IONP-LPrA2 significantly reduced leptin-induced S phase progression and cell proliferation in all breast cancer cell lines and the formation of tumorspheres in MDA-MB-231 cells.Also, IONP-LPrA2 showed an additive effect on the reduction of breast cancer cell survival with chemotherapeutics.Cis plus IONP-LPrA2 produced a significant reduction in the survival of MDA-MB-231 and HCC1806 cells.CTX plus IONP-LPrA2 caused a significant decrease in the survival of MDA-MB-231 cells.Dox plus IONP-LPrA2 caused a marked reduction in the survival of HCC1806 cells.Although, PTX plus IONP-LPrA2 did not have a major effect on the viability of the breast cancer cells when compared to PTX alone.CONCLUSION Present data indicate that IONP-LPrA2 may be a useful adjuvant for chemotherapeutic treatment of breast cancer, particularly for TNBC which lacks targeted therapeutic options.
AIM To develop a leptin peptide receptor antagonist linked to nanoparticles and determine its effect on viability of breast cancer cells. METHODS The leptin antagonist, LPrA2, was coupled via EDAC [1-Ethyl-3- (3-dimethylaminopropyl) carbodiimide] (IONP-LPrA2) to increase its efficacy .IONP-LPrA2 conjugation was confirmed by Western blot and nanoparticle tracking analysis. Human triple negative breast cancer (TNBC) MDA-MB-231, HCC1806 and estrogen receptor positive (ER +) MCF-7 cells were analyzed for the expression of the leptin receptor, Ob-R. The effects of leptin and antagonist on levels of leptin-induced STAT3 phosphorylation and cyclin D1, cell cycle progression, cell proliferation, and tumorsphere formation in breast cancer cells were determined. Doses of the chemotherapeutics [cisplatin (Cis), cyclophosphamide (CTX), doxorubicin (Dox) and paclitaxel (PTX)] to effectively reduce cell viability were calculated. The effects of combination treatments of IONP-LPrA2 and ch RESULTS: The viability of transfected cells identified as IONP-LPrA2 at approximately 100 kD.IONPLPrA2 significantly decreased leptin-induced p STAT3 levels in HCC1806 cells and drastically decreased cyclin D1 levels in all cell lines. significantly reduced leptin-induced S phase progression and cell proliferation in all breast cancer cell lines and the formation of tumorspheres in MDA-MB-231 cells. Also, IONP-LPrA2 showed an additive effect on the reduction of breast cancer cell survival with chemotherapeutics. Cis plus IONP-LPrA2 produced a significant reduction in the survival of MDA-MB-231 and HCC1806 cells. CTX plus IONP-LPrA2 caused a significant decrease in the survival of MDA-MB- 231 cells. Dox plus IONP-LPrA2 caused a marked reduction in the survival of HCC1806 cells. Although PTX plus IONP-LPrA2 did not have a major effect on the viability of the breast cancer cells when compared to PTX alone .CONCLUSION Present data indicate that IONP-LPrA2 may be a useful adjuvant for chemotherapeutic treatment of breast cancer, particularly for TNBC which lacks targeted therapeutic options.