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Dichotomous role of autophagy in cancer Cover

Dichotomous role of autophagy in cancer

Asian Biomedicine
Volume 16 (2022): Issue 3 (June 2022)
By: Amin Arif,  Muhammad Babar Khawar,  Rabia Mehmood,  Muddasir Hassan Abbasi and  Nadeem Sheikh  
Open Access
|Jun 2022

Figures & Tables

Figure 1

Schematic of autophagic routes. (A) Macroautophagy (commonly named autophagy): the autophagosome comprising several cytosolic polypeptides and proteins merges with lysosomes; subsequently, the autophagosomal content is digested by the lysosomal enzymes. (B) Microautophagy: the cytoplasmic elements directly enclosed by the inward pinching of lysosomal membrane. (C) CMA: the selective components move toward the lysosome after intermingling with the chaperone HSC70 and degrade in the lysosome. Created with BioRender.com. Academic License QJ23ZNIZN0. CMA, chaperone-mediated autophagy; PAS, preautophagosomal structure; HSC70, heat shock cognate 70 chaperones; LAMP2A, lysosome-associated membrane glycoprotein type 2A.

Figure 2

Schematic of macroautophagy flux. Autophagy starts with the development of a phagophore followed by the nucleation and elongation controlled by a class III PI3K complex and subsequently enclosure of cytoplasmic contents or organelles to form an autophagosome. The autophagosome then merges with a lysosome to develop into an autophagolysosome, the ultimate site for degradation and recycling. mTOR negatively controls autophagic flux, and it is inhibited by rapamycin and AZD8055 to induce autophagy. Beclin-2 also negatively controls autophagy by inhibiting the PI3K complex, and obatoclax and gossypol inhibit Beclin-2. 3-Methyladenine and wortmannin are early-stage inhibitors that hinder autophagy by negative control of the class III PI3K, and chloroquine, hydroxychloroquine, and biflomycin A are late-stage inhibitors that block the autophagic flux by interfering with the lysosome directly. Created with BioRender.com. Academic License DS23ZNI6O2. mTOR, mammalian targets of rapamycin; PI3K, phosphatidylinositol 3-kinase; CQ, chloroquine; HCQ, hydroxychloroquine.

Autophagy regulators used in cancer therapy

Autophagy regulatorTypeMode of actionReferences
3-MethyladenineInhibitorP13K inhibitorsUpregulation of p62 protein expression[60, 70, 71, 72]
WortmanninInhibit phagosome formation[70, 73, 74]
LY294002Promote apoptosis[71, 75]
ChloroquineLysosome inhibitorsPrevent acidification[76]
HydroxychloroquineInhibit autophagosome accumulationInhibit the formation of autolysosome[77, 78, 79, 80]
Bafilomycin AInhibit autophagic degradation[81]
TioconazolATG inhibitorsInhibit phagophore elongation[82]
FMK-9aInhibit autophagosome fusion[83]
RapamycinInducermTOR inhibitorsPrevent inactivation of ULK1 phosphorylation[84]
AZD8055Activate or induce autophagyInduction of apoptosisCell cycle arrest[85, 86]
Vitamin DNatural products or mTOR inhibitorsIncrease intestinal calcium absorptionInduce expression of proapoptotic proteinsInduces an autophagic transcriptional signatureInduce autophagosome formation[87, 88]
ResveratrolInduce apoptotic cell deathSuppress growth of cancer cell[89]
CurcuminInduce apoptosisInhibit phosphorylation of AKT[90]
ObatoclaxBH3 Mimetics or Beclin-2 inhibitorsBcl-2 inhibition[91, 92]
GossypolROS productionAutophagic-mediated necroptosis[93]
DOI: https://doi.org/10.2478/abm-2022-0014 | Journal eISSN: 1875-855X | Journal ISSN: 1905-7415
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Language: English
Page range: 111 - 120
Published on: Jun 30, 2022
Published by: Chulalongkorn University
In partnership with: Paradigm Publishing Services
Publication frequency: 6 issues per year
Keywords:
autophagy,
carcinogenesis,
neoplasms,
pathology,
recycling therapeutics
Related subjects:
Medicine,
Assistive professions, nursing,
Basic medical science,
Basic medical science, other,
Clinical medicine,
Clinical medicine, other

© 2022 Amin Arif, Muhammad Babar Khawar, Rabia Mehmood, Muddasir Hassan Abbasi, Nadeem Sheikh, published by Chulalongkorn University
This work is licensed under the Creative Commons Attribution 4.0 License.

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