Department: Medicinal Chemistry Department
Public PhD Defence date: 16th November 2022
Doctoral Thesis title: Metabolomic approach to understand the mechanism of metformin-induced PRODH/POX-dependent apoptosis in MCF-7 breast cancer cells
Supervisor: Prof. dr hab. Jerzy Pałka (Chief of the Department of Medicinal Chemistry)
Reviewers: Prof. dr hab. Anna Jelińska (Dean of the Faculty of Pharmacy, MUP),
Prof. dr hab. Marcin Kołaczkowski (Head of the Department of Medicinal Chemistry, Faculty of Pharmacy),
Prof. dr hab. Michal Piotr Marszałł (Head of the Department and Department of Drug Chemistry at the Faculty of Pharmacy Collegium Medicum, UMK)
Current affiliation: University of Alabama at Birmingham, USA
Plans for the Future: seeking for Postdoc position in EU/US/UK
Abstract of the Doctoral Thesis:
The objective of the study is to evaluate the mechanism of Metformin-induced apoptosis in MCF-7 breast cancer cells. It involves the induction of proline dehydrogenase/proline oxidase (PRODH/POX)-dependent ROS generation under the availability of proline, the PRODH/POX substrate, in specific nutrient conditions.
Metformin treatment and PRODH/POX knockout decreased the proliferation of MCF-7 cells and strongly suppressed the proliferation in a glutamine-free medium. In addition, Metformin induced expression of AMPK, cleaved PARP, and caspase 7 in both cell lines. In the absence of glutamine, Metformin treatment or PRODH/POX-knock out of MCF-7 cells contributed to similar inhibition of glycolysis and increased utilization of metabolites of TCA and UC, contributing to apoptosis. However, in the presence of glutamine, Metformin treatment or PRODH/POX-knock out of MCF-7 cells contributed to utilizing studied metabolites (except glucose).
It suggests that in the absence of glutamine, Metformin treatment or PRODH/POX-knock out contributed to glucose starvation and apoptosis in MCF-7 cells. The results provide insight into Metformin's anticancer activity on MCF-7 breast cancer cells.