Accumulation of esterified cholesterol (cholesteryl ester) in lipid droplets of high-grade prostate cancer (PCa) and PCa metastases may aid in the diagnosis and treatment of advanced disease, researchers have discovered.
“Our study provides an avenue toward diagnosis of aggressive prostate cancer,” investigator Ji-Xin Cheng, PhD, of Purdue University, said in a university statement. “Moreover, we showed that depleting cholesteryl ester significantly impairs prostate cancer aggressiveness.”
As Dr. Cheng and colleagues explained in Cell Metabolism (2014;19:393-406), altered lipid metabolism is increasingly recognized as a signature of cancer cells. The team found an unexpected, aberrant accumulation of esterified cholesterol in human PCa tissue. Biochemical analysis revealed that this accumulation resulted from the loss of the tumor-suppressing gene PTEN and the subsequent activation of the P13K/AKT pathway in PCa cells, promoting tumor growth.
Dr. Cheng’s group then used the drugs avasimibe and Sandoz 58-035 to deplete cholesteryl ester storage. These agents significantly hindered advanced PCa growth in laboratory cell cultures and in xenograft mouse models: They significantly reduced cancer proliferation, impaired cancer-invasion capability, and suppressed tumor growth, with negligible toxicity.
When originally developed as a treatment for atherosclerosis, avasimibe and Sandoz 58-035 showed a lack of effectiveness in reducing plaque size, and clinical trials were halted. Dr. Cheng pointed out, however, that their study “highlights a novel use of these drugs to treat advanced prostate cancer.”