Targeting Production of Reactive Oxygen Species as an Anticancer Strategy

Marioli-Sapsakou, Grigoria-Kalliopi; Kourti, Malamati

doi:10.21873/anticanres.15408

Cited by 6 publications

(4 citation statements)

References 149 publications

(203 reference statements)

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“…Especially mitochondria-dependent intrinsic apoptosis is closely associated with the loss of mitochondrial membrane potential (ΔΨm) that is resulted in mitochondrial membrane permeabilization and the production of ROS [ 41 , 42 ]. Sequentially, highly increasing ROS also act as inducers of apoptotic cell death in various types of cells, including fibroblast cells [ 41 , 42 , 43 ]. In addition, the increasing ROS induce the increase of autophagosome [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

25-Hydroxycholesterol-Induced Oxiapoptophagy in L929 Mouse Fibroblast Cell Line

et al. 2021

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25-hydroxycholesterol (25-HC) is an oxysterol synthesized from cholesterol by cholesterol-25-hydroxylase during cholesterol metabolism. The aim of this study was to verify whether 25-HC induces oxiapoptophagy in fibroblasts. 25-HC not only decreased the survival of L929 cells, but also increased the number of cells with condensed chromatin and altered morphology. Fluorescence-activated cell sorting results showed that there was a dose-dependent increase in the apoptotic populations of L929 cells upon treatment with 25-HC. 25-HC-induced apoptotic cell death was mediated by the death receptor-dependent extrinsic and mitochondria-dependent intrinsic apoptosis pathway, through the cascade activation of caspases including caspase-8, -9, and -3 in L929 cells. There was an increase in the levels of reactive oxygen species and inflammatory mediators such as inducible nitric oxide synthase, cyclooxygenase-2, nitric oxide, and prostaglandin E2 in L929 cells treated with 25-HC. Moreover, 25-HC caused an increase in the expression of beclin-1 and microtubule-associated protein 1A/1B-light chain 3, an autophagy biomarker, in L929 cells. There was a significant decrease in the phosphorylation of protein kinase B (Akt) in L929 cells treated with 25-HC. Taken together, 25-HC induced oxiapoptophagy through the modulation of Akt and p53 cellular signaling pathways in L929 cells.

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Section: Discussionmentioning

confidence: 99%

25-Hydroxycholesterol-Induced Oxiapoptophagy in L929 Mouse Fibroblast Cell Line

et al. 2021

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“…Upregulation of ROS induces apoptosis in various cell types and is related to autophagosome formation ( Caillot et al, 2021 ; Marioli-Sapsakou and Kourti, 2021 ; Michallet et al, 2011 ). Autophagy is a fundamental physiological process in all living cells that breaks down intracellular components, such as unnecessary or damaged organelles and protein aggregates, and transports them to the lysosomes for recycling ( Chun and Kim, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

7α,25-Dihydroxycholesterol-Induced Oxiapoptophagic Chondrocyte Death via the Modulation of p53-Akt-mTOR Axis in Osteoarthritis Pathogenesis

Seo

Kim

Kang

et al. 2023

Molecules and Cells

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This study aimed to exploring the pathophysiological mechanism of 7α,25-dihydroxycholesterol (7α,25-DHC) in osteoarthritis (OA) pathogenesis. 7α,25-DHC accelerated the proteoglycan loss in ex vivo organ-cultured articular cartilage explant. It was mediated by the decreasing extracellular matrix major components, including aggrecan and type II collagen, and the increasing expression and activation of degenerative enzymes, including matrix metalloproteinase (MMP)-3 and -13, in chondrocytes cultured with 7α,25-DHC. Furthermore, 7α,25-DHC promoted caspase-dependent chondrocyte death via extrinsic and intrinsic pathways of apoptosis. Moreover, 7α,25-DHC upregulated the expression of inflammatory factors, including inducible nitric oxide synthase, cyclooxygenase-2, nitric oxide, and prostaglandin E 2 , via the production of reactive oxygen species via increase of oxidative stress in chondrocytes. In addition, 7α,25-DHC upregulated the expression of autophagy biomarkers, including beclin-1 and microtubule-associated protein 1A/1B-light chain 3 via the modulation of p53-Akt-mTOR axis in chondrocytes. The expression of CYP7B1, caspase-3, and beclin-1 was elevated in the degenerative articular cartilage of mouse knee joint with OA. Taken together, our findings suggest that 7α,25-DHC is a pathophysiological risk factor of OA pathogenesis that is mediated a chondrocyte death via oxiapoptophagy, which is a mixed mode of apoptosis, oxidative stress, and autophagy.

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“…Platinum-based anti-cancer drugs, including OXP, can lead to the production of intracellular ROS in both direct and indirect manners and further oxidative stress-induced cytotoxicity [ 49 , 50 , 51 , 52 ]. Nonetheless, the majority of cancer cells exhibit elevated levels of ROS due to an augmented metabolic rate, genetic mutation, and a state of relative hypoxia [ 53 , 54 ], which is attributed as a cause of metabolic reprogramming [ 55 , 56 ].…”

Section: Discussionmentioning

confidence: 99%

Quercetin-Induced Glutathione Depletion Sensitizes Colorectal Cancer Cells to Oxaliplatin

Lee

Jang

Kim

et al. 2023

Foods

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Quercetin is an antioxidant phytochemical which belongs to the natural flavonoids group. Recently, the compound has been reported to inhibit glutathione reductase responsible for replenishing reduced forms of glutathione and thus leads to glutathione depletion, triggering cell death. In this study, we examined if quercetin sensitizes tumors to oxaliplatin by inhibiting glutathione reductase activity in human colorectal cancer cells, and thereby facilitates apoptotic cell death. A combined treatment with quercetin and oxaliplatin was found to synergistically inhibit glutathione reductase activity, lower intracellular glutathione level, increase reactive oxygen species production, and reduce cell viability, compared to treatment with oxaliplatin alone in human colorectal HCT116 cancer cells. Furthermore, the incorporation of sulforaphane, recognized for its ability to scavenge glutathione, in combination with quercetin and oxaliplatin, substantially suppressed tumor growth in an HCT116 xenograft mouse model. These findings suggest that the depletion of intracellular glutathione by quercetin and sulforaphane could strengthen the anti-cancer efficacy of oxaliplatin.

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Targeting Production of Reactive Oxygen Species as an Anticancer Strategy

Cited by 6 publications

References 149 publications

25-Hydroxycholesterol-Induced Oxiapoptophagy in L929 Mouse Fibroblast Cell Line

25-Hydroxycholesterol-Induced Oxiapoptophagy in L929 Mouse Fibroblast Cell Line

7α,25-Dihydroxycholesterol-Induced Oxiapoptophagic Chondrocyte Death via the Modulation of p53-Akt-mTOR Axis in Osteoarthritis Pathogenesis

Quercetin-Induced Glutathione Depletion Sensitizes Colorectal Cancer Cells to Oxaliplatin

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