PURPOSE: Resistance to endocrine and chemotherapies remains the primary cause of breast cancer treatment failure. We have synthesized four novel D: -erythro N-octanoyl sphingosine analogs and catalogued their activity in drug-sensitive (MCF-7), endocrine-resistant (MDA-MB-231) and chemoresistant (MCF-7TN-R) breast cancer cells. METHODS: 3-(4,5-Dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine cell viability; colony assay was performed to determine effects on clonogenic survival and (1)H NMR, (13)C NMR, HPLC spectra and elemental analytical data analyses were used to determine analog identity and purity. RESULTS: All four analogs inhibited both viability and clonogenic survival, with analog C exhibiting a log-fold improvement in anti-survival activity compared to the parent compound. CONCLUSION: With resistance to current breast cancer chemotherapies on the rise, the development of novel therapeutic targets is of growing importance. Our results show that lipid analogs have therapeutic potential in treating chemo- and endocrine-resistant breast cancer.
PURPOSE: Resistance to endocrine and chemotherapies remains the primary cause of breast cancer treatment failure. We have synthesized four novel D: -erythro N-octanoyl sphingosine analogs and catalogued their activity in drug-sensitive (MCF-7), endocrine-resistant (MDA-MB-231) and chemoresistant (MCF-7TN-R) breast cancer cells. METHODS:3-(4,5-Dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine cell viability; colony assay was performed to determine effects on clonogenic survival and (1)H NMR, (13)C NMR, HPLC spectra and elemental analytical data analyses were used to determine analog identity and purity. RESULTS: All four analogs inhibited both viability and clonogenic survival, with analog C exhibiting a log-fold improvement in anti-survival activity compared to the parent compound. CONCLUSION: With resistance to current breast cancer chemotherapies on the rise, the development of novel therapeutic targets is of growing importance. Our results show that lipid analogs have therapeutic potential in treating chemo- and endocrine-resistant breast cancer.
Authors: Adharsh P Ponnapakam; Jiawang Liu; Kaustubh N Bhinge; Barbara A Drew; Tony L Wang; James W Antoon; Thong T Nguyen; Patrick S Dupart; Yuji Wang; Ming Zhao; Yong-Yu Liu; Maryam Foroozesh; Barbara S Beckman Journal: Bioorg Med Chem Date: 2014-01-08 Impact factor: 3.641
Authors: James W Antoon; Melyssa R Bratton; Lori M Guillot; Scott Wadsworth; Virgilio A Salvo; Matthew E Burow Journal: Cancer Biol Ther Date: 2012-07-24 Impact factor: 4.742
Authors: Bridgette M Collins-Burow; James W Antoon; Daniel E Frigo; Steven Elliott; Christopher B Weldon; Stephen M Boue; Barbara S Beckman; Tyler J Curiel; Jawed Alam; John A McLachlan; Matthew E Burow Journal: J Steroid Biochem Mol Biol Date: 2012-05-24 Impact factor: 4.292
Authors: James W Antoon; Martin D White; Evelyn M Slaughter; Jennifer L Driver; Hafez S Khalili; Steven Elliott; Charles D Smith; Matthew E Burow; Barbara S Beckman Journal: Cancer Biol Ther Date: 2011-04-01 Impact factor: 4.742
Authors: James W Antoon; Melyssa R Bratton; Lori M Guillot; Scott Wadsworth; Virgilio A Salvo; Steven Elliott; John A McLachlan; Matthew E Burow Journal: Am J Cancer Res Date: 2012-06-28 Impact factor: 6.166