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 (KD), 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.
Original language | English |
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Pages (from-to) | 912-917 |
Number of pages | 6 |
Journal | Carcinogenesis |
Volume | 37 |
Issue number | 9 |
DOIs | |
State | Published - Sep 1 2016 |