Epoxyazadiradione Induced Apoptosis/Anoikis in Triple‐Negative Breast Cancer Cells, MDA‐MB‐231, by Modulating Diverse Cellular Effects

Abstract

Triple‐negative breast cancer (TNBC) is one of the most aggressive forms of its kind,which accounts for 15–20% of all breast cancers. As this cancer form lacks hormonereceptors, targeted chemotherapy remains the best treatment option. Apoptosisand anoikis (detachment‐induced cell death) induction by small molecules canprevent TNBC metastasis to a greater extent. Epoxyazadiradione (EAD) is a limo-noid from the neem plant with an anticancer property. Here, we demonstrate thatEAD induced mitochondria‐mediated apoptosis and anoikis in TNBC cells (MDA‐MB‐231). Apart from this, it promotes antimigration, inhibition of colony formation,downregulation of MMP‐9 and fibronectin, induction of G2/M phase arrest withdownregulation of cyclin A2/cdk2, interference in cellular metabolism, and inhibi-tion of nuclear factor kappa‐B (NF‐KB) nuclear translocation. Moreover, a significantreduction is observed in the expression of EGFR on the plasma membrane andnucleus upon treatment with EAD. Among the diverse cellular effects, anoikis in-duction, metabolic interference, and downregulation of membrane/nuclear EGFRexpression by EAD are reported here for the first time. To summarize, EAD targetsmultiple cellular events to induce growth arrest in TNBC, and hence can bedeveloped into the best antineoplastic agent in the future.