Serum 5-LOX: A progressive protein marker for breast cancer and new approach for therapeutic target

Rahul Kumar, Abhay Kumar Singh, Manoj Kumar, Shashank Shekhar, Nitish Rai, Punit Kaur, Rajinder Parshad, Sharmistha Dey

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

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 languageEnglish
Pages (from-to)912-917
Number of pages6
JournalCarcinogenesis
Volume37
Issue number9
DOIs
StatePublished - Sep 1 2016

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