Isolation, purification and characterization of naturally derived Crocetin beta-D-glucosyl ester from Crocus sativus L. against breast cancer and its binding chemistry with ERalpha and HDAC2

Abstract Saffron plant (Crocus sativus L.) is being used as a source of saffron spice and medicine cure or prevent different types of diseases including cancers. We report the isolation, characterization of bioactive small molecule ([crocetin (β-D-glucosyl) ester] from the leaf biowastes saffron plant of Kashmir, India. MTTC assay and Bio-autography aided approach were used to assess anticancer activity and anti-cancer properties of crocin (s) against DPPH free radical and breast cancer cell line respectively. Crocetin beta-D-glucosyl ester restrained proliferation of human breast adeno-carcinoma cell model (MCF-7) without significantly affecting normal cell line (L-6). This is further explained using molecular docking based predicted binding affinity of crocetin beta-D-glucosyl ester with known breast cancer targets ERalpha and HDAC2. The studies involving molecular mechanics generalized born surface area and molecular docking showed that crocetin beta-D-glucosyl ester exhibits strong affinity for estrogen receptor alpha and histone deacetylase 2 (crucial receptors involved in breast cancer signalling) as reflected by the negative docking score and binding free energy (BFE) values. Therefore, crocetin beta-D-glucosyl ester from Crocus sativus biowastes showed antiproliferative effect possibly by inhibiting estrogen receptor alpha and HDAC2 mediated signaling cascade.