Autophagy-related genes are induced by histone deacetylase inhibitor suberoylanilide hydroxamic acid via the activation of cathepsin B in human breast cancer cells
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Han Han1,2, Jing Li1, Xiuyan Feng1,3, Hui Zhou1, Shanchun Guo4,5 and Weiqiang Zhou1
1Key Laboratory of Environmental Pollution and Microecology of Liaoning Province, Shenyang Medical College, Huanggu, Shenyang City, Liaoning Province 110034, P. R. China
2Department of Biochemistry and Molecular Biology, Shenyang Medical College, Huanggu, Shenyang City, Liaoning Province 110034, P. R. China
3The Second Affiliated Hospital of Shenyang Medical College, Heping, Shenyang City, Liaoning Province 110002, P. R. China
4RCMI Cancer Research Center, Xavier University of Louisiana, New Orleans, LA 70125, USA
5Department of Chemistry, Xavier University of Louisiana, New Orleans, LA 70125, USA
Weiqiang Zhou, email: [email protected]
Keywords: SAHA, autophagy, apoptosis, cathepsin B, cell cycle
Received: November 02, 2016 Accepted: May 10, 2017 Published: June 08, 2017
Autophagy is involved in modulating tumor cell motility and invasion, resistance to epithelial-to-mesenchymal transition, anoikis, and escape from immune surveillance. We have previous shown that SAHA is capable to induce several apoptosis and autophagy-related gene expression in breast cancers. However, the exact mechanisms of autophagy activation in this context have not been fully identified. Our results showed that the expression and the activity of Cathepsin B (CTSB), one of the major lysosomal cysteine proteases, were significantly increased in MDA-MB- 231 and MCF-7 cells upon SAHA treatment. We confirmed that Cystatin C, a protease inhibitor, significantly inhibited the expression of CTSB induced by SAHA on breast cancer cells. We demonstrated that SAHA is able to promote the expression of LC3II, a key member in the maturation of the autophagosome, the central organelle of autophagy in breast cancer cells. However, SAHA induced LC3II expression is effectively suppressed after the addition of Cystatin C to the cell culture. In addition, we identified a number of genes, as well as the mitogen-activated protein kinase (MAPK) signaling that is potentially involved in the action of SAHA and CTSB in the breast cancer cells. Overall, our results revealed that the autophagy-related genes are induced by SAHA via the activation of CTSB in breast cancer cells. An improved understanding of SAHA molecular mechanisms in breast cancer may facilitate SAHA clinical use and the selection of suitable combinations.
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