Stearoyl-CoA-Desaturase 1 inhibition induces apoptosis in Pancreatic Cancer cells

Pancreatic cancer (PC) is an aggressive cancer with advanced disease at diagnosis and lack of effective therapy. PC tumours carry a mutated KRAS gene essential to their growth and spread, which plays a key role in deregulating cell metabolism. Stearoyl-CoA-Desaturase 1 (SCD1) is a highly regulated enzyme responsible for desaturating fatty acids, converting Stearic acid to Oleic acid. The expression of SCD1 is known to be upregulated in PC, indicating that it represents a metabolic bottleneck for cancer cell metabolism and might contribute to the growth and spread of PC. The aim of this study is to determine the effects of inhibiting SCD1 activity on a PC cell line (PANC1) in vitro. PANC1 cells were incubated for 48 hours with various concentrations of CAY10566, a selective SCD1 inhibitor. The cells were trypsinized, stained with Annexin V (AnV) and Propidium Iodide (PI) and analysed using flow cytometry. SCD1 inhibition (INHIB) significantly decreases viable PANC1 cells (AnV-, PI-) compared to a medium-only control (CON) (INHIB 48.76% (± 0.03), CON 60.71% (±0.01), P<0.05) and significantly increased apoptosis (AnV +, PI-) (INHIB 31.56% (±0.07), CON 25.32% (±0.02), P<0.05. Microscopically, the membrane of these cells appears less defined after treatment with the SCD inhibitor, indicating changes in composition may occur. Our results show that SCD1 inhibition significantly affects PC cell death and apoptosis. Further work is required to combine SCD1 inhibition with the standard PC chemotherapy Gemcitabine, and assess if there is a synergistic effect of the two drugs. This supplemented treatment could improve TMN (tumour metastasis node) and progression free survival, both clinical markers of patient outcome, in PC patients.