International Journal of Biomedical and Clinical Sciences Vol. 1, No. 2, 2016, pp. 30-35 http://www.aiscience.org/journal/ijbcs * Corresponding author E-mail address: zhossain@nccu.edu (Md. Z. Hossain) Characterization of Key Molecular Mechanisms and Biological Pathways Involved in Wortmannin Induced Breast Cancer MCF-7 Programmed Cell Death Rozina Akter 1 , Michael A. Gealt 2 , Maurice G. Kleve 3 , Md. Zakir Hossain 4, * 1 Department of Applied Biosciences, University of Arkansas at Little Rock, Little Rock, Arkansas, USA 2 Central Michigan University, Mount Pleasant, Michigan, USA 3 Department of Biology, University of Arkansas at Little Rock, Little Rock, Arkansas, USA 4 Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and Technology Enterprise (BRITE), North Carolina Central University, Durham, North Carolina, USA Abstract The present study aimed to explore the molecular mechanisms and biological pathways involved in Wortmannin induced breast cancer MCF-7 programmed cell death. The direct cellular and molecular effect of Wtmn was investigated selectively on the MCF-7 cancer cell line. To study morphological effects phase contrast microscopy was used. The mitochondrial membrane potential and detection of caspase activity were investigated using fluorescent microscopy. Our morphological, molecular, and caspases expression indicated the intrinsic apoptosis pathways involved, and confirmed the role of Wtmn in these pathways. Our experimental results demonstrated that Wortmannin (Wtmn), an irreversible and selective PI3-K inhibitor, inhibits the proliferation of MCF-7 breast cancer cells, and facilitates their entry into apoptosis. Our data established the anti-cancer properties of Wtmn on MCF-7 breast cancer cells. These studies directed us towards elucidating the molecular mechanisms and biological pathways mainly involved in this process. This findings offer potential drug screening to search for novel inducers of apoptosis on MCF-7 cells, and could be used to design better drugs. Keywords MCF-7, Wortmannin, Caspase, Mitochondrial Membrane Potential, and Apoptosis Received: May 19, 2016 / Accepted: May 28, 2016 / Published online: September 10, 2016 @ 2016 The Authors. Published by American Institute of Science. This Open Access article is under the CC BY license. http://creativecommons.org/licenses/by/4.0/ 1. Introduction Breast carcinoma is the most common malignancy as well as high morbidity in women worldwide [1-2]. Although several biological properties of Wtmn have been identified, the precise molecular mechanisms underlying its action on cytotoxicity and cell death appear unknown to date. Novel and advanced alternative therapeutic strategies are needed. Studies reported that Wtmn exhibits anti-tumor effects on human breast cancer cell lines in vivo, but the details mechanism of action of cell death are not with the MCF-7 contexts, specifically in the apoptotic programmed cell death perspective in-vitro [3-7]. Therefore, the goal of this research had a specific aim to elucidate the molecular mechanisms and biological pathways involved in Wtmn induced MCF-7 cancer cell death. In most eukaryotes, mitochondria are not only the power house of cellular energy production but also play crucial role in regulating or initiating apoptotic cell