Table 2 The effects of reactive oxygen species (ROS) in paraptosis
From: Exploring paraptosis as a therapeutic approach in cancer treatment
Small molecules or treatments | Cancer types | Causes of ROS increase | Affected signaling pathways | References |
|---|---|---|---|---|
Auranofin | Breast cancer cells (MDA-MB-435S)# | Inhibit TrxR1 enzyme activity, proteasome activity Decrease GSH levels | Induce ER stress (upregulate p-eIF2α, CHOP) Activate ATF4/CHAC1 axis leads to GSH degradation | [107] |
Curcuminoid B63 | Gastric cancer cells (SGC-7901, BGC-823, SNU-216) | Inhibit TrxR1 activity | Induce ER stress (upregulate p-eIF2α, CHOP, ATF4) Activate MAPK pathway (p38, ERK, JNK) | [30] |
CPYPP Curcumin Cyclosporin | Melanoma (MDA-MB-435), breast cancer cells (MDA-MB-231) | Impair thiol homeostasis | Induce ER stress (upregulate CHOP, ATF3, ATF4, GADD34, GADD45α, PERK, IRE1α, HERPUD1, BiP) Increase CDK7 and CDK9 activity Upregulate protein kinase K, heat shock proteins | [36] |
δ-Tocotrienol (δ-TT) | Melanoma cells (A375, BLM) | Induce Ca2+ overload Downregulate OXPHOS complex I, decrease oxygen consumption and mitochondrial membrane potential | Activate MAPK (p38, ERK, JNK) Inhibit ATP synthesis | [42] |
Jolkinolide B | Bladder cancer cells (T24, UM-UC-3) | Inhibit TrxR1 enzyme activity without change protein, depletion of glutathione | Induce ER stress (upregulate ATF4, CHOP) Activate MAPK (p38, ERK, JNK) | [39] |
Nitrovin | Glioblastoma multiforme (U251, U87) | Inhibit thioredoxin reductase (TrxR1) activity without changing TrxR1 protein | Induce ER stress (upregulate p-eIF2α, CHOP, ATF4, BiP) Activate MAPK (p38, ERK, JNK) | [40] |
Me2NNMe2 | Colorectal cancer (SW480, HCT-116) | Inhibit disulfide isomerase (PDI) activity and disturb endoplasmic reticulum thiol redox homeostasis | Activate MEK–ERK pathway Induce ER stress (upregulate PERK, p-eIF2α, ero1L-α, CHOP) | [29] |
Withaferin A | Breast cancer lines: MCF-7, MDA-MB-231 | Promote the hyperpolarization of mitochondrial membrane potential | Induce ER stress (upregulate CHOP, BiP) | [44] |
Honokiol | Acute promyelocytic leukemia (NB4 cells) | Promote the depolarization of mitochondrial membrane potential | Induce ER stress (upregulate Bip, CHOP) Activate mTOR, MAPK (p38, ERK, JNK) | [37] |
YRL1091, pyrazolo[3,4-h]quinoline derivative | Breast cancer cells (MDA-MB-231, MCF-7) | Increase ROS | Induce ER stress (upregulate ATF4, CHOP, BiP) Activate MAPK (ERK, JNK) | [113] |