August 1, 2018 Source: MedicalNewsToday 106
Based on studies that have revealed how specific malignancies thrive on cholesterol, and that raised serum cholesterol levels are linked to the risk of cancer and a drug compound called leelamine that has shown to retard tumor-growth in melanoma, researchers headed by Omer Kuzu, a postdoctoral fellow in pharmacology at the Pennsylvania State University Cancer Institute in Hershey aspired to hamper the transport of cholesterol within treatment-resistant cancer cells.
To achieve this, they tested 42 functional inhibitors of acid sphingomyelinase (FIASMAs) that were either antipsychotics or antidepressants and contrasted their effects to those of leelamine.
Kuzu and his team tested the drugs primarily in cell cultures, and later in mouse models of melanoma.
Perphenazine and fluphenazine among the 42 drugs were found to be equally effective as leelamine at destroying cancer cells.
The researchers then orally administered these drugs to mice and supervised the size and weight of the rodents' tumors. It was seen that Perphenazine decreased the size and weight of the tumors in such high doses that made the rodents sleepy.
"Perphenazine was able to decrease tumor growth by shutting down cholesterol metabolism in cancer cells," explains Kuzu. "But the problem was that the drug concentrations required to do so led to sedative effects and loss of animal weight since mice were sleeping and not eating."
Subsequently, the scientists used nanoparticles made of lipids, called nanoliposomes to deliver the drug and prevent side effects.
The nano drug transporters administered intravenously killed the tumors without producing as many side effects as they could not permeate the blood-brain barrier like the oral drugs.
"This study suggests that disruption of intracellular cholesterol transport by targeting ASM [acid sphingomyelinase] could be utilized as a potential chemotherapeutic approach for treating cancer," conclude the authors.By Ddu
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