Seminar in Medicine, 28.04.2017, Assoc. Prof. Ceyda Açılan AyhanAuthor: KUSOM
Location: MED 176
Speaker : Assoc. Prof. Ceyda Açılan Ayhan / TUBITAK, Marmara Research Center - Genetic Engineering and Biotechnology Institute
TelePresence : AH Dean's Office / KUH 9th floor Meeting Room
Chromosomal Segregation Defects in Cancer Cells and Metal Based Agents as a Platform in Cancer Therapy
The primary research goals in our laboratory are directed towards understanding the molecular basis of chromosomal segregation defects and mechanism of action for potential anticancer drugs. The chemotherapeutics used today mostly suffer from the destructive side effects on healthy tissues as a result of failure to selectively target tumor cells. Unlike normal cells, tumor cells frequently exhibit extra centrosomes, which tend to form multipolar spindles (MPS), leaving one/some of the cells with less genetic material triggering death pathways. Nevertheless, cancer cells divide successfully by coalescing their extra centrosomes into two poles. In our laboratory, we have shown that the mitotic kinase Nek2A has a role in centrosomal unclustering. Hence, one of our major aims is to identify novel Nek2A targets, and determine which one of these targets play a role in centrosome clustering. This way, selective killing of cancer cells exhibiting supernumerary centrosomes may be possible through poisons towards those targets, and our findings will be translated in the clinic.
The second project that is ongoing in our lab is characterization of anticancer drugs and investigation of their molecular mechanism of action. Metal based chemotherapeutic drugs are widely used as an effective method to defeat various cancers. In this talk, I will describe our data on a novel therapeutic agent: a Palladium(II) Saccharinate Complex of Terpyridine. We showed that the complex was more cytotoxic to various types of cancer cells in comparison to non-cancer controls and induced apoptosis. It also effectively reduced tumor size and appeared to cause less side effects compared to cisplatin. To better understand this agent, we performed nano LC-MS/MS analyses in human breast cancer cells. The data was suggestive of increased double strand breaks (DSBs). The presence of DSBs was confirmed in vitro and in cell culture. There was also increased intracellular reactive oxygen species (ROS) formation. Scavenging ROS rescued cell death in response to Pd(II) treatment, potentially explaining how the Pd(II) complex damaged the DNA. The complex was also found to be cell cycle non-specific to exert its toxicity. The details of this analysis and the significance will be discussed during the scope of this work.