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European Journal of Pharmaceutical Sciences
journal homepage: www.elsevier.com/locate/ejps
Autophagy as a molecular target for cancer treatment
Nur Mehpare Kocaturka, Yunus Akkocb, Cenk Kigc, Oznur Bayraktard, Devrim Gozuacika,b, Ozlem Kutlua,
a Sabanci University Nanotechnology Research and Application Center (SUNUM), Istanbul 34956, Turkey
b Faculty of Engineering and Natural Sciences, Molecular Biology, Genetics and Bioengineering Program, Sabanci University, Istanbul 34956, Turkey
c Faculty of Medicine, Istanbul Yeni Yuzyil University, Zeytinburnu, 34010 Istanbul, Turkey
d Faculty of Medicine, Department of Medical Biology and Genetic, Okan University, Istanbul, Turkey
Chemical compounds studied in this article:
Epigallocatechin gallate (EGCG) (PubChem CID: 65064)
Hidroxychloroquine (PubChem CID: 3652)
Suberoylanilide Hydroxamic acid (SAHA)
Autophagy is an evolutionarily conserved catabolic mechanism, by which eukaryotic cells recycle or degrades internal constituents through membrane-traﬃcking pathway. Thus, autophagy provides the cells with a sus-tainable source of biomolecules and energy for the maintenance of homeostasis under stressful conditions such as tumor microenvironment. Recent findings revealed a close relationship between autophagy and malignant transformation. However, due to the complex dual role of autophagy in tumor survival or cell death, eﬀorts to develop eﬃcient treatment strategies targeting the autophagy/cancer relation have largely been unsuccessful. Here we review the two-faced role of autophagy in cancer as a tumor suppressor or as a pro-oncogenic me-chanism. In this sense, we also review the shared regulatory pathways that play a role in autophagy and ma-lignant transformation. Finally, anti-cancer therapeutic agents used as either inhibitors or inducers of autophagy have been discussed.
Corresponding author at: Sabanci University Nanotechnology Research and Application Center (SUNUM), Orta Mah. Univ. Cad. No: 27, Istanbul 34956, Turkey. E-mail address: [email protected] (O. Kutlu).
Autophagy is a catabolic process in which cytoplasmic materials are directed to the lysosomes for degradation. This process is evolutionarily conserved from yeast to man and its activity is required for maintaining cellular homeostasis through elimination of dysfunctional organelles, protein aggregates or even long-lived proteins. So far, three main classes of autophagy have been identified: Macroautophagy, micro-autophagy and chaperon-mediated autophagy (CMA). Macroautophagy (autophagy herein) is the main pathway that is devided into bulk and
selective autophagy according to the specificity of targeted cytoplasmic constituents. In bulk autophagy, degradation targets are mainly wrapped within a double-membraned vesicle (autophagosome) as portions of cytoplasm in a non-selective manner. On the other hand, in selective autophagy particular substrate such as mitochondria (Okamoto et al., 2009), peroxisomes (Till et al., 2012), lysosomes (Hung et al., 2013), ER (Khaminets et al., 2015), ribosomes (An and Harper, 2018), lipid droplets (Onal et al., 2017), pathogenic in-tracellular invaders (Wileman, 2013) and even certain free proteins and RNAs (Huang et al., 2014b) are targeted into the autophagosome. In