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Role of lysosomes in cancer therapy

Authors Halaby R

Received 19 May 2015

Accepted for publication 20 July 2015

Published 28 September 2015 Volume 2015:6 Pages 147—155

DOI https://doi.org/10.2147/RRB.S83999

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Professor Zvi Kelman

Reginald Halaby

Department of Biology, Montclair State University, Montclair, NJ, USA

Abstract: Lysosomes are acidic organelles that are involved in cellular digestion by endocytosis, phagocytosis, and autophagy. They contain more than 50 hydrolases that are capable of degrading all macromolecules. There is accumulating evidence that lysosomal enzymes can provoke apoptotic cell death. This has important implications for cancer, where proapoptotic genes are mutated and antiapoptotic genes are often overexpressed leading to chemoresistance. Lysosomes play a dual role in cancer development depending on their subcellular localization. When they are located extracellularly they can promote invasion, angiogenesis, and metastasis. However, when they are located intracellularly they can trigger apoptosis by leaking into the cytosol. In this review, we examine the pathways by which lysosomes can evoke both apoptosis and tumorigenesis. Although cancer cells have defects in their apoptotic machinery, they can still undergo lysosomal cell death. We offer several strategies to explain how targeting lysosomes can serve as a putative model for the development of novel anticancer agents. Furthermore, we propose that lysosomal cell death is an effective treatment against apoptosis-resistant cancer cells and thus holds great potential as a therapeutic strategy for circumventing apoptosis deficiency in tumors.

Keywords: cathepsins, lysosomal membrane permeability, apoptosis, chemoresistance
 

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