I-Chen Kung
Taipei Medical University, Taiwan
Title: A novel synthetic LSD1 inhibitor with anticancer activity in Prostate cancer cells
Biography
I-Chen Kung graduated from the Department of Medical Laboratory Science and Biotechnology, Taipei Medical University. I am a medical technologist in Taiwan. Due to get to know pharmacology, pharmacy, pharmacokinetics during my college year, I am interested in chemotherapy of cancer. Therefore, I decided to study in the pharmacy field. Now, I am a master student in the Institute of Pharmacy, Taipei Medical University and a member in the Clinical drug discovery lab. Although the knowledge of pharmacy is less for me, I will study hard and combine with my profession. I wish that I can find a novel compound or a new signaling pathway to treat cancer.
Abstract
In the United States during 2018, an estimated 164,690 new cases and 29,430 deaths of prostate cancer. Prostate cancer ranks as the first of new cases and the second of deaths from cancer in the US during 2018. The lysine-specific demethylase 1A (LSD1/KDM1A) is the first histone demethylase discovered and it can remove mono- or di-methyl groups from lysine K4 or K9 on histone H3. LSD1 expression is increased in malignant prostate cancer. Overexpression of LSD1 enhances cell growth and cancer metastasis. Therefore, we want to treat prostate cancer by inhibiting cell growth or inducing cell death or suppressing cell migration and epithelial–mesenchymal transition (EMT) through the inhibition of LSD1. We synthesize a new compound (Compound X) for LSD1 inhibition, and we compare with a well-known LSD1 inhibitor, SP2509. SP2509 can inhibit cell growth in prostate cancer cell PC3 and DU145 with micromolar GI50 value (1.34 and 2.12 ïM), and Compound X can inhibit cell growth in PC3 and DU145 with submicromolar GI50 value (0.34 and 0.89 ïM) by SRB assay. Our results show that Compound X induces sub G1 phase of cell cycle arrest in a time-dependent manner and induces caspase-dependent apoptosis and inhibits migration and EMT more than SP2509 in PC3 and DU145 cells. Knockdown of LSD1 enhances Compound X-induced cell apoptosis and suppression of migration in PC3 and DU145 cells. It has been reported that N-myc downstream-regulated gene 1 (NDRG1) is a potent metastatic suppressor in prostate and colon cancer cells. Our data show that Compound X increase NDRG1 expression, therefore we will investigate if NDRG1 plays an important role in the inhibition of migration and EMT by treated with Compound X. These data show that our new Compound X has more potent than well-known LSD1 inhibitor, SP2509.