Antioxidant Therapy in Cancer: Rationale and Progress

Antioxidants, Journal Year: 2022, Volume and Issue: 11(6), P. 1128 - 1128

Published: June 8, 2022

Cancer is characterized by increased oxidative stress, an imbalance between reactive oxygen species (ROS) and antioxidants. Enhanced ROS accumulation, as a result of metabolic disturbances signaling aberrations, can promote carcinogenesis malignant progression inducing gene mutations activating pro-oncogenic signaling, providing possible rationale for targeting stress in cancer treatment. While numerous antioxidants have demonstrated therapeutic potential, their clinical efficacy remains unproven. Here, we review the for, recent advances in, pre-clinical research on antioxidant therapy cancer, including with nonenzymatic antioxidants, such NRF2 activators, vitamins, N-acetylcysteine GSH esters, or enzymatic NOX inhibitors SOD mimics. In addition, will offer insights into prospective options improving effectiveness therapy, which may expand its applications

Language: Английский

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Drug-induced oxidative stress in cancer treatments: Angel or devil?

Redox Biology, Journal Year: 2023, Volume and Issue: 63, P. 102754 - 102754

Published: May 18, 2023

Oxidative stress (OS), defined as redox imbalance in favor of oxidant burden, is one the most significant biological events cancer progression. Cancer cells generally represent a higher level, which suggests dual therapeutic strategy by regulating status (i.e., pro-oxidant therapy and/or antioxidant therapy). Indeed, exhibits great anti-cancer capability, attributing to accumulation within cells, whereas restore homeostasis has been claimed fail several clinical practices. Targeting vulnerability pro-oxidants capable generating excessive reactive oxygen species (ROS) surfaced an important strategy. However, multiple adverse effects caused indiscriminate attacks uncontrolled drug-induced OS on normal tissues and drug-tolerant capacity some certain greatly limit their further applications. Herein, we review representative oxidative drugs summarize side organs, emphasizing that seeking balance between damage value exploiting next-generation OS-based chemotherapeutics.

Language: Английский

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Epithelial–mesenchymal transition: The history, regulatory mechanism, and cancer therapeutic opportunities

MedComm, Journal Year: 2022, Volume and Issue: 3(2)

Published: May 18, 2022

Abstract Epithelial–mesenchymal transition (EMT) is a program wherein epithelial cells lose their junctions and polarity while acquiring mesenchymal properties invasive ability. Originally defined as an embryogenesis event, EMT has been recognized crucial process in tumor progression. During EMT, cell–cell cell–matrix attachments are disrupted, the cytoskeleton remodeled to enhance mobility of cells. This phenotype largely driven by group key transcription factors, typically Snail, Twist, ZEB, through epigenetic repression markers, transcriptional activation matrix metalloproteinases, reorganization cytoskeleton. Mechanistically, orchestrated multiple pathways, especially those involved such TGFβ, Wnt, Hedgehog, Hippo, suggesting intrinsic link between embryonic development cancer In addition, redox signaling also emerged critical modulator. confers with increased metastatic potential drug resistant capacity, which accounts for recurrence most clinic cases. Thus, targeting can be therapeutic option providing chance cure patients. Here, we introduce brief history summarize recent advances understanding mechanisms, well highlighting opportunities treatment.

Language: Английский

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Mecheliolide elicits ROS-mediated ERS driven immunogenic cell death in hepatocellular carcinoma

Redox Biology, Journal Year: 2022, Volume and Issue: 54, P. 102351 - 102351

Published: May 28, 2022

The nonnegligible reason for the poor prognosis of hepatocellular carcinoma (HCC) is resistance to conventional chemotherapy. Immunogenic cell death (ICD) a rare immunostimulatory form that can reengage tumor-specific immune system. ICD improve clinical outcomes chemotherapeutics by promoting long-term cancer immunity. discovery potential inducers emerging as promising direction. In present study, micheliolide (MCL), natural guaianolide sesquiterpene lactone, was screened out virtual screening strategies, identified an inhibitor thioredoxin reductase (TrxR) and evaluated have high induce ICD. Here, we showed MCL induced ICD-associated DAMPs (damage-associated molecular patterns, such CRT exposure, ATP secretion HMGB1 release). significantly triggered regression established tumors in immunocompetent mouse vaccine model, (DCs maturation, stimulation CD4+, CD8+ T-cells responses) vivo. Mechanistically, found magnitude effects upon exposure HCC cells dependent on generation reactive oxygen species (ROS)-mediated endoplasmic reticulum stress (ERS). addition, suppression ROS normalized MCL-induced ERS, contrast, downregulation TrxR synergized with ERS driven MCL. We also systematically detected H2O2 using Hyper7 sensors exposed Notably, inhibited development organoids. Collectively, our results reveal association between inhibitors ICD, presenting valuable insights into MCL-activated cells.

Language: Английский

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Redox signaling at the crossroads of human health and disease

MedComm, Journal Year: 2022, Volume and Issue: 3(2)

Published: March 31, 2022

Abstract Redox biology is at the core of life sciences, accompanied by close correlation redox processes with biological activities. homeostasis a prerequisite for human health, in which physiological levels nonradical reactive oxygen species (ROS) function as primary second messengers to modulate signaling orchestrating multiple sensors. However, excessive ROS accumulation, termed oxidative stress (OS), leads biomolecule damage and subsequent occurrence various diseases such type 2 diabetes, atherosclerosis, cancer. Herein, starting evolution biology, we reveal roles multifaceted modulators mediate sustain homeostasis. In addition, also emphasize detailed OS mechanisms involved initiation development several important diseases. double‐edged sword disease progression suggest two different therapeutic strategies treat redox‐relevant diseases, targeting sources redox‐related effectors manipulate will largely promote precision medicine. Therefore, comprehensive understanding networks under pathological conditions facilitate medicine benefit patients

Language: Английский

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CRISPR screens uncover protective effect of PSTK as a regulator of chemotherapy-induced ferroptosis in hepatocellular carcinoma

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Jan. 4, 2022

Abstract Background Hepatocellular carcinoma (HCC) is among the most common forms of cancer and associated with poor patient outcomes. The emergence therapeutic resistance has hampered efficacy targeted treatments employed to treat HCC patients date. In this study, we conducted a series CRISPR/Cas9 screens identify genes synthetic lethality capable improving clinical responses. Methods CRISPR-based loss-of-function genetic were used target 18,053 protein-coding in cells chemotherapy-related lethal these cells. Synergistic effects analyzed through vitro vivo analyses, while related mechanisms explored RNA-seq metabolomics analyses. Potential inhibitors identified targets selected high-throughput virtual screening. Results inhibition phosphoseryl-tRNA kinase (PSTK) was found increase cell sensitivity chemotherapeutic treatment. PSTK suppression chemotherapy-induced ferroptosis cells, depletion resulted inactivation glutathione peroxidative 4 (GPX4) disruption (GSH) metabolism owing selenocysteine cysteine synthesis, thus enhancing induction upon Punicalin, an agent hepatitis B virus (HBV), as possible inhibitor that exhibited synergistic when applied together Sorafenib vivo. Conclusions These results highlight key role for mediator treatment functions by suppressing ferroptotic induction. may represent ideal candidates overcoming drug HCC.

Language: Английский

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Redox dyshomeostasis strategy for tumor therapy based on nanomaterials chemistry

Chemical Science, Journal Year: 2022, Volume and Issue: 13(8), P. 2202 - 2217

Published: Jan. 1, 2022

This review summarizes the current progress of redox dyshomeostasis (RDH) strategy for tumor therapy. makes cells more sensitive to therapy patterns through using nanomaterials disrupt homeostasis.

Language: Английский

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Radiotherapy-mediated redox homeostasis-controllable nanomedicine for enhanced ferroptosis sensitivity in tumor therapy

Acta Biomaterialia, Journal Year: 2023, Volume and Issue: 159, P. 300 - 311

Published: Jan. 13, 2023

Language: Английский

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β-Sitosterol as a Promising Anticancer Agent for Chemoprevention and Chemotherapy: Mechanisms of Action and Future Prospects

Advances in Nutrition, Journal Year: 2023, Volume and Issue: 14(5), P. 1085 - 1110

Published: May 27, 2023

Cancer is one of the primary causes death worldwide, and its incidence continues to increase yearly. Despite significant advances in research, search for effective nontoxic preventive therapeutic agents remains greatly important. a multimodal disease, where various mechanisms play roles occurrence progression. This highlights need multitargeted approaches that are not only safe inexpensive but also provide alternatives current regimens. β-Sitosterol (SIT), most abundant phytosterol found plant foods, represents such an option. Preclinical evidence over past few decades has overwhelmingly shown SIT exhibits multiple anticancer activities against varied cancers, as liver, cervical, colon, stomach, breast, lung, pancreatic, prostate addition leukemia, myeloma, melanoma, fibrosarcoma. In this article, we present latest perspectives on SIT-systematically summarizing antitumor action into 7 main sections combining challenges prospects-for use promising agent cancer prevention treatment. particular, plays role treatment mainly by enhancing apoptosis, inducing cell cycle arrest, bidirectionally regulating oxidative stress, improving metabolic reprogramming, inhibiting invasion metastasis, modulating immunity inflammation, combating drug resistance. Although holds great promise, poor aqueous solubility bioavailability coupled with low targeting efficacy limit clinical application. Further research novel delivery systems may improve these deficiencies. Overall, through complex pleiotropic mechanisms, good potential tumor chemoprevention chemotherapy. However, no trials have yet proven potential. review provides theoretical basis rationality further design conduct confirm activity SIT.

Language: Английский

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Thioredoxin (Trx): A redox target and modulator of cellular senescence and aging-related diseases

Redox Biology, Journal Year: 2024, Volume and Issue: 70, P. 103032 - 103032

Published: Jan. 21, 2024

Thioredoxin (Trx) is a compact redox-regulatory protein that modulates cellular redox state by reducing oxidized proteins. Trx exhibits dual functionality as an antioxidant and cofactor for diverse enzymes transcription factors, thereby exerting influence over their activity function. has emerged pivotal biomarker various diseases, particularly those associated with oxidative stress, inflammation, aging. Recent clinical investigations have underscored the significance of in disease diagnosis, treatment, mechanistic elucidation. Despite its paramount importance, intricate interplay between senescence-a condition characterized irreversible growth arrest induced multiple aging stimuli-remains inadequately understood. In this review, our objective to present comprehensive up-to-date overview structure function Trx, involvement signaling pathways senescence, association age-related well potential therapeutic target. Our review aims elucidate novel extensive role senescence while highlighting implications diseases.

Language: Английский

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