Peer-reviewed veterinary case report
How simvastatin affects growth of canine tumor cells
By Kobayashi, Kosuke et al.·Published in Veterinary and comparative oncology·2021·The United Graduate School of Veterinary Science, Japan·View original on PubMed →
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Original publication title: Effect of simvastatin on cell proliferation and Ras activation in canine tumour cells.
- Species:
- dog
Plain-English summary
A study looked at how simvastatin, a medication commonly used to lower cholesterol, affects tumor cells in dogs. Researchers found that simvastatin slowed the growth of various canine tumor cells, including those from hemangiosarcoma and melanoma, by causing cell death and stopping the cells from dividing. The treatment worked by reducing certain proteins that help tumors grow. While simvastatin showed promise in fighting these types of cancer cells, it did not have the same effect on lymphoma cells. More research is needed to fully understand how simvastatin can help treat different types of canine tumors.
People also search for: dog cancer treatment simvastatin · hemangiosarcoma in dogs · melanoma treatment for dogs
Abstract
Statins are inhibitors of the mevalonate cascade that is responsible for cholesterol biosynthesis and the formation of intermediate metabolites, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) used in the prenylation of proteins. Although statins are widely used in the treatment of hypercholesterolemia, recent studies suggest that they also inhibit proliferation of tumour cells by reducing prenylation of small GTP-binding proteins, such as, Ras. This study aimed to evaluate the effect of simvastatin on cell proliferation and Ras activation in various canine tumour cell lines, including hemangiosarcoma (HSA), melanoma, and lymphoma cell lines. Simvastatin inhibited cell proliferation of all cell lines tested in a concentration- and time-dependent manner, but the susceptibilities were different amongst the cell lines. Simvastatin induced apoptotic cell death via activation of caspase-3 and cell cycle arrest. The cytotoxic effects of simvastatin were attenuated by GGPP and FPP. Simvastatin decreased the amount of prenylated Ras and GTP-bound Ras in HSA and melanoma cell lines, but not in lymphoma cell lines. These results indicate that simvastatin induces cytotoxic effects through the depletion of GGPP and FPP in a variety of canine tumour cells, whereas multiple mechanisms are involved in the effects. Further study is required to elucidate the underlying mechanisms of simvastatin-induced cytotoxic effects in a variety of canine tumour cells.
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Search related cases →Original publication on PubMed: https://pubmed.ncbi.nlm.nih.gov/32779819/