1. Assessment of acyl-CoA cholesterol acyltransferase (ACAT-1) role in ovarian cancer progression—An in vitro study
- Author
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Vijayalakshmi N. Ayyagari, Paula L. Diaz-Sylvester, Kathleen Groesch, Laurent Brard, and Xinjia Wang
- Subjects
0301 basic medicine ,Apoptosis ,Biochemistry ,Small hairpin RNA ,Prostate cancer ,Oxidative Damage ,0302 clinical medicine ,Cell Movement ,Medicine and Health Sciences ,Cell Cycle and Cell Division ,Acetyl-CoA C-Acetyltransferase ,RNA, Small Interfering ,Tumor Stem Cell Assay ,Staining ,Caspase 7 ,Membrane Potential, Mitochondrial ,Ovarian Neoplasms ,Multidisciplinary ,Cell Death ,Chemistry ,Caspase 3 ,Cell Cycle ,Cell Staining ,Lipids ,Ovarian Cancer ,Cholesterol ,Oncology ,Cell Processes ,030220 oncology & carcinogenesis ,Disease Progression ,Medicine ,Female ,Cholesterol Esters ,Research Article ,Cell Survival ,Science ,Sterol O-acyltransferase ,Research and Analysis Methods ,03 medical and health sciences ,Pancreatic cancer ,Cell Line, Tumor ,medicine ,Humans ,Neoplasm Invasiveness ,Cell Cycle Inhibitors ,Cell Proliferation ,Cell growth ,Cancer ,Cancers and Neoplasms ,Biology and Life Sciences ,Cell Biology ,medicine.disease ,030104 developmental biology ,Specimen Preparation and Treatment ,Cancer research ,Cisplatin ,Ovarian cancer ,Reactive Oxygen Species ,Gynecological Tumors ,Sterol O-Acyltransferase - Abstract
Abnormal accumulation of acyl-CoA cholesterol acyltransferase-1 (ACAT-1) mediated cholesterol ester has been shown to contribute to cancer progression in various cancers including leukemia, glioma, breast, pancreatic and prostate cancers. However, the significance of ACAT-1 and cholesterol esters (CE) is relatively understudied in ovarian cancer. In this in vitro study, we assessed the expression and contribution of ACAT-1 in ovarian cancer progression. We observed a significant increase in the expression of ACAT-1 and CE levels in a panel of ovarian cancer cell lines (OC-314, SKOV-3 and IGROV-1) compared to primary ovarian epithelial cells (normal controls). To confirm the tumor promoting capacity of ACAT-1, we inhibited ACAT-1 expression and activity by treating our cell lines with an ACAT inhibitor, avasimibe, or by stable transfection with ACAT-1 specific short hairpin RNA (shRNA). We observed significant suppression of cell proliferation, migration and invasion in ACAT-1 knockdown ovarian cancer cell lines compared to their respective controls (cell lines transfected with scrambled shRNA). ACAT-1 inhibition enhanced apoptosis with a concurrent increase in caspases 3/7 activity and decreased mitochondrial membrane potential. Increased generation of reactive oxygen species (ROS) coupled with increased expression of p53 may be the mechanism(s) underlying pro-apoptotic action of ACAT-1 inhibition. Additionally, ACAT-1 inhibited ovarian cancer cell lines displayed enhanced chemosensitivity to cisplatin treatment. These results suggest ACAT-1 may be a potential new target for the treatment of ovarian cancer.
- Published
- 2020