title: Anticancer drugs for the modulation of endoplasmic reticulum stress and oxidative stress.
abstract: Prior research has demonstrated how the endoplasmic reticulum (ER) functions as a multifunctional organelle and as a well-orchestrated protein-folding unit. It consists of sensors which detect stress-induced unfolded/misfolded proteins and it is the place where protein folding is catalyzed with chaperones. During this folding process, an immaculate disulfide bond formation requires an oxidized environment provided by the ER. Protein folding and the generation of reactive oxygen species (ROS) as a protein oxidative byproduct in ER are crosslinked. An ER stress-induced response also mediates the expression of the apoptosis-associated gene C/EBP-homologous protein (CHOP) and death receptor 5 (DR5). ER stress induces the upregulation of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) receptor and opening new horizons for therapeutic research. These findings can be used to maximize TRAIL-induced apoptosis in xenografted mice. This review summarizes the current understanding of the interplay between ER stress and ROS. We also discuss how damage-associated molecular patterns (DAMPs) function as modulators of immunogenic cell death and how natural products and drugs have shown potential in regulating ER stress and ROS in different cancer cell lines. Drugs as inducers and inhibitors of ROS modulation may respectively exert inducible and inhibitory effects on ER stress and unfolded protein response (UPR). Reconceptualization of the molecular crosstalk among ROS modulating effectors, ER stress, and DAMPs will lead to advances in anticancer therapy.
authors.affiliation: Institute of Biomedical and Genetic Engineering (IBGE), KRL Hospital, Islamabad, Pakistan, ammadfarooqi@rlmclahore.com.
authors.forename: Ammad Ahmad
authors.initials: AA
authors.lastname: Farooqi
authors.forename: Kun-Tzu
authors.initials: KT
authors.lastname: Li
authors.forename: Sundas
authors.initials: S
authors.lastname: Fayyaz
authors.forename: Yung-Ting
authors.initials: YT
authors.lastname: Chang
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ismail
authors.forename: Chih-Chuang
authors.initials: CC
authors.lastname: Liaw
authors.forename: Shyng-Shiou F
authors.initials: SS
authors.lastname: Yuan
authors.forename: Jen-Yang
authors.initials: JY
authors.lastname: Tang
authors.forename: Hsueh-Wei
authors.initials: HW
authors.lastname: Chang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D059865:Endoplasmic Reticulum Stress / Q000235:genetics*; D006801:Humans; D051379:Mice; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D018384:Oxidative Stress / Q000235:genetics; D017510:Protein Folding; D017382:Reactive Oxygen Species / Q000378:metabolism*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C497249:DDIT3 protein, human; D017382:Reactive Oxygen Species; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D051742:Transcription Factor CHOP