Posted on March 21, 2018

Qatar University College of Health Sciences (QU-CHS) graduate in biomedical sciences Lubna Al-Zaidan conducted a master’s thesis project on “Screening novel molecular targets of metformin in breast cancer by proteomic approach”.

The study found that metformin induced Apoptosis in both breast adenocarcinoma and breast normal cell lines with minimal toxicity in normal breast cells. Metformin also resulted in cell cycle arrest at G1 phase in breast adenocarcinoma cell line via decreasing Cyclin Dependent Kinases (CDKs) and the upregulation of Retinoblastoma (Rb) related proteins (p107 and p130). Lubna Al-Zaidan noted that proteomics analysis revealed that the induction of apoptosis by metformin in breast adenocarcinoma cell line was via the intrinsic caspase independent signaling pathway through upregulation of Endonuclease G (ENDO-G) and Apoptosis-inducing factor (AIF). She said: “Metformin also induced endoplasmic reticulum stress and subsequent apoptotic cell death via the activation the proapoptotic family members.”

She added: “Metformin upregulated activated protein kinase (AMPK) in breast adenocarcinoma resulting in subsequent inhibition of the mammalian target of rapamycin (mTOR). Furthermore, mTOR was downregulated in breast adenocarcinoma treated cells which consequently decreases protein synthesis. Several potential therapeutic targets were revealed such as Growth Regulation by Estrogen in Breast Cancer1 (GREB1), MAP kinase interacting serine/threonine-protein kinase 1 (MKNK1) and Emopamil Binding Protein (EBP) that can be utilized in the development of new therapies.”

She also noted that metformin exerts its effect on several cellular processes inducing apoptotic cell death and cell cycle arrest. She said: “Metformin indeed may offer supportive role in cancer therapeutic regimens as a neoadjuvant drug for treatment of breast cancer.” The project won the Award of Outstanding Thesis at QU Annual Research Forum & Exhibition 2017 and was published in Frontiers in Public Health journal. It was supervised by CHS Associate Dean for Academic Affairs Dr Ahmed Malki.