67th Annual Meeting Abstracts
Lipitor (Atorvastatin) Induces Autophagy And Causes Cell Death In Prostate Cancer Cells
*Ankur Parikh
Geisinger Medical Center, Danville, PA
Introduction: Autophagy, or “self-eating”, is a process of intracellular molecular degradation, in which targeted cellular components are engulfed by autophagosomes and delivered to lysosomes (or vacuoles) for degradation. The autophagic process is activated under nutritional stress and has been shown an important role in cancer cell growth. Lipitor (Atorvastatin) is an inhibtor of HMG-CoA reductase, a key enzyme in synthesis of cholesterol, and a broadly prescribed medication for reduction of blood cholesterol. Because Lipitor is a metabolic inhibitor, we explored the idea that treatment of Lipitor induces autophagy and inhibits cancer cell growth in prostate cancer cells.
Materials & Methods: PC-3, an androgen receptor-negative prostate cancer cell line, was used in experiments. Autophagy in response to Lipitor treatment was determined by detection of cellular level of LC3-II, an autophagosomal marker, via immunoblotting of the cell lysates with anti-LC-3 antibody. Lipitor-induced autophagic process was further analyzed with various autophagy inhibitors. The effect of Lipitor on PC-3 cell growth was determined by cell viability assay and cell number counting.
Results: Lipitor treatment on PC-3 cells for 40 hrs had an approximately 11-fold increase in LC3-II expression compared with control, and increased expression of LC3-II occurred with Lipitor in a dose-dependent manner, indicating that Lipitor induces autophagy in prostate cancer cells. Treatment with Lipitor at concentrations within prescribed medication dosage caused rapid death of the prostate cancer cells, raising a possibility in application of Lipitor for prostate cancer therapy.
Conclusions: Lipitor induces autophagy and causes cancer cell death in prostate cancer cells.
