Imminent Angiotensin‑converting Enzyme Inhibitor from Microbial Source for Cancer Therapy

Abstract

Background: Drugs targeting Angiotensin I‑converting enzyme (ACE) have been used broadly in cancer chemotherapy. The recent past coupled with our results demonstrates the effective use of ACE inhibitors (ACEi) as anticancer agents, and they are potentially relevant in deriving new inhibitors.

Methods: Bacterial strains were isolated from cow milk collected in Coimbatore, Tamil Nadu, India and plated on nutrient agar medium. The identity of the strain was ascertained by 16s rRNA gene sequencing method and was submitted to the NCBI GenBank nucleotide database. Various substrates were screened for ACEi production by the fermentation with the isolated strain. ACEi was purifed by sequential steps of ethanol precipitation, ion exchange column chromatography and gel fltration column chromatography. The apparent molecular mass was determined by SDSPAGE. The anticancer property was analyzed by studying the cytotoxicity effects of ACEi using Breast cancer MCF‑7 cell lines.

Results: The isolate coded as BUCTL09 was selected and identifed
as Micrococcus luteus. Among the seven substrates, only beef extract fermented broth showed an inhibition of 79% and was reported as the best substrate. The peptide was purifed and molecular mass was determined. The IC50 value of peptide was found to be 59.5 µg/ ml. The purifed peptide has demonstrated to induce apoptosis of cancer cell.

Conclusions: The results of this study revealed that Peptide has been determined as an active compound that inhibited the activity of ACE. These properties indicate the possibilities of the use of purifed protein as a potent anticancer agent.

Keywords: 16S rRNA gene sequence, angiotensin‑converting enzyme inhibitor, anticancer activity, antimetastatic, antiproliferative, beef extract, hippuric acid, MCF‑7 cell line, Micrococcus luteus