Influence of N-alkynylaminosteroids on mitochondria function and autophagy in glioma cells

Author:

Panada J.U.1,Klopava V.A.1,Kulahava T.A.2,Faletrov Y.V.3,Frolova N.S.1,Koran S.V.4,Fomina E.G.4,Shkumatov V.M.3

Affiliation:

1. Research Institute for Physical Chemical Problems of the Belarusian State University, Minsk, Belarus

2. Institute for Nuclear Problems of the Belarusian State University, Minsk, Belarus

3. Research Institute for Physical Chemical Problems of the Belarusian State University, Minsk, Belarus; Belarusian State University, Minsk, Belarus

4. Republican Research and Practical Center for Epidemiology and Microbiology, Minsk, Belarus

Abstract

In this work we examined the synthesized N-alkynyl-17-aminosteroids and N-alkynyl-20-aminosteroids (based on dehydroepiandrosterone and pregnenolone, respectively) for their effect on C6 rat glioma cell functions. At 10 μM, the compounds had an insignificant effect on C6 glioma mitochondrial membrane potential, but increased cell autophagy by 70-90%, comparable to the known autophagy inducer dexamethasone. Docking simulations predict a potential high-affinity interaction between N-alkynylaminosteroids and Keap1 and the Hedgehog pathway protein, Smoothened, which are involved in autophagy regulation. The possible mechanisms of observed processes are discussed.

Publisher

Institute of Biochemistry

Subject

General Biochemistry, Genetics and Molecular Biology,General Medicine

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