Archives

  • 2022-06
  • 2022-05
  • 2022-04
  • 2021-03
  • 2020-08
  • 2020-07
  • 2018-07
  • br T br Nur Mehpare

    2022-06-21

    
    T
    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 L-Glutathione Reduced (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 L-Glutathione Reduced 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).
    Keywords:
    Autophagy
    Cancer
    Therapeutic agents
    1. Introduction
    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
    Fig. 1. Molecular mechanism of autophagy regulation in mammals.
    Autophagic process consists of several phases such as initiation (A), nucleation (B), maturation (C), fusion and degradation (D). Same colours express the involvement of proteins or molecules in respective complexes or pathways.
    this review, we mainly focus on autophagy and other major classes, CMA and microautophagy were discussed in detailed elsewhere (Kaushik and Cuervo, 2018; Oku and Sakai, 2018).
    The ability to recycle macromolecules through autophagy gives cells an advantage for survival under stressful conditions such as nutrient starvation, oxidative stress, hypoxia, ER stress, metabolic stress etc. (Piacentini and Kroemer, 2015). Moreover, selective autophagy allows cells to control number of the organelles based on the requirement, eliminating dysfunctional compartments and disposing of pathogens by combining the ubiquitin-proteasome system (UPS) and autophagic machinery (Kocaturk and Gozuacik, 2018). However, under certain conditions excess or deregulated activity of autophagy may also lead cell death. Whether autophagy is an executioner or a savior is still a matter of debate and it is often determined in a context- and cell type-dependent manner (Liu et al., 2016).