Anticancer and Chemosensitizing Effects of WEE‐1 Kinase Inhibitor MK‐1775 in Triple Negative (MB‐231) Breast Cancer Cells

Abstract

Current breast cancer classification included cells that express estrogen (ER) and progesterone (PR) receptors, those with ERBB2 (HER‐2/Neu) amplification, and those without expression of ER, PR, or amplification of ERBB2 (referred to as triple‐negative or basal‐like breast cancer). Triple negative breast cancers are generally more difficult to treat, are known to be more aggressive and with poor prognosis. Several molecular mechanisms have been identified as potential targets for development of drugs to treat breast cancer including cell cycle checkpoints kinases. The G2/M cell‐cycle protein tyrosine kinase, Wee‐1, plays a crucial role in the checkpoint arrest for DNA repair before mitotic entry. Under normal conditions, cells repair damaged DNA during G1 arrest; however, cancer cells often have a deficient G1/S (p53) checkpoint and depend on a functional G2/M checkpoint for DNA repair. MK‐1775 is a well‐characterized Wee‐1 kinase inhibitor with significant evidence supporting its potential use as anti‐cancer and/or chemosensitizing drug. Working hypothesis proposed for this project was that use of Wee‐1 kinase inhibitors in breast cancer cells can result in profound and significant anticancer and chemosensitizing effects. In order to test this hypothesis, we show previously in a series of dose response experiments using DNA‐Damaging agents or treatments (DNA‐dt: Ex. Cisplatin, 5‐Fluororacil and Doxorubicin) alone and/or in combination with MK‐1775. To continue testing this hypothesis an Immunoblotting bioassay is currently developed for continue monitoring the effects of MK‐1775 in several biochemical markers in triple negative breast cancer cell line. Preliminary results indicated that biochemical marker in triple negative cell line, are time dependent with the different combination of DNA‐dt alone and/or in combination with MK‐1775. Initial preliminary results indicated taken together, our preliminary results are consistent with a potential role of Wee‐1 kinase inhibitors like MK‐17175 as anticancer and/or chemosensitizing agents against triple‐negative or basal‐like breast cancer cells.Support or Funding InformationThe project described was supported by NIGMS/INBRE award P20 GM103475; U.S. Department of Education Title V grant number P031S130068 and Puerto Rico Science Technology and Research Trust. The content is solely the responsibility of the authors and does not necessarily represent the official view of any of the supporting agencies.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.