Mucuna pruriens (L.) DC chemo sensitize human breast cancer cells via downregulation of prolactin-mediated JAK2/STAT5A signaling

L-Dopa (LD) in Mucuna pruriens (L.) DC gets converted into dopamine (DA) by DOPA decarboxylase (DDC) enzyme. DA binds to the DA receptor subtype 2 (DRD2), which by coupling with inhibitory heterotrimeric G proteins (Gi and Go), results in the inhibition of production and secretion of prolactin (PRL). Unavailable to prolactin receptor (PRLR), PRL is unable to induce their dimerization leading to blockade of series of events including, PRLR phosphorylation, activation of JAK2 and subsequent activation of STAT5A protein which further activates promoter of Cyclin D1 and would otherwise lead to the increased cellular proliferation of breast cancer cells. Further, MP when combined with Cisplatin (Pt) inhibits otherwise activated PRL-mediated JAK2 pathway, reduces glutathione-s-transferase (GST) activity and allow Cisplatin to enter into the nucleus and form abduct with DNA, increasing the efficacy of cisplatin as compared to its administration alone in breast cancer cells.372