title: Serum 5-LOX: a progressive protein marker for breast cancer and new approach for therapeutic target.
abstract: Lipoxygenase (LOX) pathway has emerged to have a role in carcinogenesis. There is an evidence that both 12-LOX and 5-LOX have procarcinogenic role. We have previously reported the elevated level of serum 12-LOX in breast cancer patients. This study evaluated the serum level of 5-LOX in breast cancer patients and its in vitro inhibition assessment with peptide inhibitor YWCS. The level of 5-LOX was determined by surface plasmon resonance (SPR). The peptide inhibitor of 5-LOX was designed by molecular modeling and kinetic assay was performed by spectrophotometry. The siRNA mediated 5-LOX gene silencing was performed to investigate the effect on proliferation of MDA-MB-231, breast cancer cell line. The serum 5-LOX level in breast cancer (5.69±1.97ng/µl) was almost 2-fold elevated compared to control (3.53±1.0ng/µl) (P < 0.0001). The peptide YWCS had shown competitive inhibitory effects with IC50, 2.2 µM and dissociation constant (K D), 4.92×10(-8) M. The siRNA mediated knockdown of 5-LOX, resulted in the decreased gene expression for 5-LOX and increased cell death in MDA-MB-231 cell line and thereby play a key role in reducing tumor proliferation. Thus, it can be concluded that 5-LOX is one of the potential serum protein marker for breast cancer and a promising therapeutic target for the same.
authors.forename: Rahul
authors.initials: R
authors.lastname: Kumar
authors.forename: Abhay Kumar
authors.initials: AK
authors.lastname: Singh
authors.forename: Manoj
authors.initials: M
authors.lastname: Kumar
authors.forename: Shashank
authors.initials: S
authors.lastname: Shekhar
authors.forename: Nitish
authors.initials: N
authors.lastname: Rai
authors.forename: Punit
authors.initials: P
authors.lastname: Kaur
authors.affiliation: Department of Biophysics and Department of Surgery, All India Institute of Medical Sciences, New Delhi 110029, India.
authors.forename: Rajinder
authors.initials: R
authors.lastname: Parshad
authors.forename: Sharmistha
authors.initials: S
authors.lastname: Dey
mesh_terms: D000328:Adult; D001094:Arachidonate 5-Lipoxygenase / Q000097:blood* / Q000502:physiology; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D008875:Middle Aged; D062105:Molecular Docking Simulation; D013053:Spectrophotometry
chemical_list: D014408:Biomarkers, Tumor; D016859:Lipoxygenase Inhibitors; D001094:Arachidonate 5-Lipoxygenase