Antiproliferative potential of bioactive molecule from Murraya koenigii L. Spreng against breast cancer: In vitro and in vivo studies and gene expression analyses

Abstract

The curry leaf extract is known to have anticancer property against breast cancer. Identification of the specific compound therein the curry leaf and its validation is essential for successful discovery of drugs. In that content, here, we extracted oleoresin from the mature curry leaves was subjected to antioxidant fractionation using column chromatography. Fraction obtained using 60:40 hexane and ethyl acetate solvent system, showing the maximum inhibition of DPPH, was subfractionated and those with the highest antioxidant property was analyzed in LC-MS/MS. Spectrum of molecules identified, along with FDA approved drugs, were docked with target proteins for breast cancer. In vitro screening of candidate phytocompounds doxylamine, histidinol and pheniramine, in their commercially available form, through Trypan blue exclusion assay against murine cancer cell lines EAC and DLA had shown that they have no cytotoxicity. Pheniramine maleate salt (PMS), doxylamine succinate salt (DSS) and L-histidinol dihydrochloride (LHD) have shown dose-dependent inhibition of proliferation of MCF-7 cells, with 280 μg/mL PMS at 72 h of incubation giving the maximum of 98.46%. Acute toxicity studies in Swiss albino mice (100 mg PMS/kg body wt.) have confirmed that the drug has no toxicity. Mouse mammary pad tumour model has shown that PMS significantly reduces the WBC count in the tumour induced mice. Liver function tests, histopathological analyses of liver, mammary pad and kidney tissues and expression analysis of oncogenes ER-α1, Bcl-2, c-Myc and Pin1 have confirmed the drug candidature of PMS.