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Thomas Jefferson University

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Full-Text Articles in Life Sciences

Mechanisms Of Simvastatin Myotoxicity: The Role Of Autophagy Flux Inhibition., Arya Emami, Shahla Shojaei, Simone C. Da Silva Rosa, Mahmoud Aghaei, Ehsan Samiei, Amir Reza Vosoughi, Forouh Kalantari, Philip Kawalec, James Thliveris, Pawan Sharma, Amir A. Zeki, Mohsen Akbari, Joseph W. Gordon, Saeid Ghavami Aug 2019

Mechanisms Of Simvastatin Myotoxicity: The Role Of Autophagy Flux Inhibition., Arya Emami, Shahla Shojaei, Simone C. Da Silva Rosa, Mahmoud Aghaei, Ehsan Samiei, Amir Reza Vosoughi, Forouh Kalantari, Philip Kawalec, James Thliveris, Pawan Sharma, Amir A. Zeki, Mohsen Akbari, Joseph W. Gordon, Saeid Ghavami

Center for Translational Medicine Faculty Papers

Statins are some of the most widely used drugs worldwide, but one of their major side effects is myotoxicity. Using mouse myoblast (C2C12) and human alveolar rhabdomyosarcoma cell lines (RH30) in both 2-dimensional (2D) and 3-dimensional (3D) cell culture, we investigated the mechanisms of simvastatin's myotoxicity. We found that simvastatin significantly reduced cell viability in C2C12 cells compared to RH30 cells. However, simvastatin induced greater apoptosis in RH30 compared to C2C12 cells. Simvastatin-induced cell death is dependent on geranylgeranyl pyrophosphate (GGPP) in C2C12 cells, while in RH30 cells it is dependent on both farnesyl pyrophosphate (FPP) and GGPP. Simvastatin inhibited …