PEITC: A Resounding Molecule Averts Metastasis in Breast Cancer Cells <i>in vitro</i> by Targeting Serine/Threonine Kinase Interplay

Abstract

Background/Aim: Intricate association and aberrant activation of serine/threonine kinase (STK) family proteins like Polo-like kinase (PLK1) and Aurora kinase (Aurora A abruptly regulate mitotic entry whereas activation of PKCδ, another important member of STK family conversely induces apoptosis which is preceded by cell cycle arrest. These STKs are considered as major determinant of oncogenicity. Therefore, the contributory role of AURKA/PLK-1 axis in mitotic control and PKCδ in apoptosis control and their reciprocity in cancer research is an emerging area to explore. The present study investigated the intricate involvement of STKs in breast cancer cells (MCF-7 and MDA-MB-231) and their disruption by PEITC. Methods: Both MCF-7 and MDA-MB-231 cells were checked for clonogenic assay, cell-cycle analysis, Western blotting, TUNEL & DNA-fragmentation assay, wound healing, transwell migration assays in presence and absence of PEITC. Results: PEITC was found to increase the expression of PKCδ with subsequent nuclear translocation. Nuclear translocation of PKCδ was accompanied by inhibition of nuclear lamin vis a vis phosphorylation of Nrf2 at Ser 40 alongside nuclear accumulation of phospho-Nrf2. Activated PKCδ furthermore exerted its apoptotic effect by negatively regulating Aurora A and consequentially PLK1; indicating activation of PLK1 by Aurora A. Involvement of PEITC induced PKCδ activation and Aurora A inhibition was ascertained by using Rottlerin/Aurora A Inhibitor. Discussion & Conclusion: Natural isothiocyanates like PEITC efficiently altered the functional abilities of STKs concerning their entangled functional interplay. Such alterations in protein expression by PEITC was chaperoned with inhibition of the aggressiveness of breast cancer cells and ultimately induction of apoptosis. Funding Information: The authors are indebted to DST, Govt of India, New Delhi, INDIA for providing financial support and DIRECTOR, Chittaranjan National Cancer Institute, Kolkata, INDIA for providing infrastructural facilities. Declaration of Interests: The authors declare that they have no conflicts of interests.