Key Role of Reactive Oxygen Species (ROS) in Indirubin Derivative-Induced Cell Death in Cutaneous T-Cell Lymphoma Cells

Soltan, Marwa Yassin; Sumarni, Uly; Assaf, Chalid; Langer, Peter; Reidel, Ulrich; Eberle, Jürgen

doi:10.3390/ijms20051158

Cited by 19 publications

(20 citation statements)

References 45 publications

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“…The extrinsic apoptosis pathway is negatively regulated by antagonistic proteins. Thus, c-FLIP (cellular FLICE-inhibitory protein) serves as a competitive inhibitor of caspase-8/-10; it can bind to the DISC but does not promote effector caspase activation [23,24]. Further downstream, the family of cellular inhibitor of apoptosis proteins (cIAPs) can bind to effector caspases and thus prevent their proteolytic activity [25,26] (Figure 2).…”

Section: Induction Of Apoptosis By Death Ligandsmentioning

confidence: 99%

Countering TRAIL Resistance in Melanoma

Eberle

2019

Cancers

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Melanoma of the skin has become a prime example for demonstrating the success of targeted cancer therapy. Nevertheless, high mortality has remained, mainly related to tumor heterogeneity and inducible therapy resistance. But the development of new therapeutic strategies and combinations has raised hope of finally defeating this deadly disease. TNF-related apoptosis-inducing ligand (TRAIL) represents a promising antitumor strategy. The principal sensitivity of melanoma cells for TRAIL was demonstrated in previous studies; however, inducible resistance appeared as a major problem. To address this issue, combination strategies were tested, and survival pathway inhibitors were shown to sensitize melanoma cells for TRAIL-induced apoptosis. Finally, cell cycle inhibition was identified as a common principle of TRAIL sensitization in melanoma cells. Mitochondrial apoptosis pathways, pro- and antiapoptotic Bcl-2 proteins as well as the rheostat consisted of Smac (Second mitochondria-derived activator of caspase) and XIAP (X-linked inhibitor of apoptosis protein) appeared to be of particular importance. Furthermore, the role of reactive oxygen species (ROS) was recognized in this setting. Inducible TRAIL resistance in melanoma can be explained by (i) high levels of antiapoptotic Bcl-2 proteins, (ii) high levels of XIAP, and (iii) suppressed Bax activity. These hurdles have to be overcome to enable the use of TRAIL in melanoma therapy. Several strategies appear as particularly promising, including new TRAIL receptor agonists, Smac and BH3 mimetics, as well as selective kinase inhibitors.

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Section: Induction Of Apoptosis By Death Ligandsmentioning

confidence: 99%

Countering TRAIL Resistance in Melanoma

Eberle

2019

Cancers

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“…Recent studies showed that indirubin derivatives DKP-071 and DKP-073 can activate the apoptotic pathway in cutaneous T-cell lymphoma and melanoma cells by inducing the production of reactive oxygen species (ROS) (Soltan et al, 2019;Zhivkova et al, 2019). Oxidative stress and elevation of ROS induced by chemicals have pleiotropic deleterious effects including developmental toxicity.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the Developmental Toxicity Induced by E804 in Zebrafish Embryos

et al. 2020

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E804, a derivative of indirubin, have multi-biological activities such as anticancer and antiinflammatory activities, but little is known about its developmental toxicity. In this study, we investigated the toxicity of E804 on the developments of zebrafish embryos. Our results showed that E804 treatment caused a significant increase of the malformation rate compared with the control groups. Pericardial edema and curved body shape were the most morphological abnormalities observed in E804-treated group. The hatching rates and body length of the zebrafish larvae was significantly decreased in E804-treated groups. E804 also affect the development of heart, liver, phagocytes and vascular formation. Further studies showed that the level of reactive oxygen species was significantly increased. The activity of total superoxide dismutase decreased and the concentration of malondialdehyde were increased. Much more apoptotic cells were detected in E804-treated group, compared with the control. In addition, geneexpression results showed that the pathways of oxidative stress and apoptosis were provoked in E804 treated groups. Taken together, our findings will be helpful to understanding E804-induced developmental toxicity and the underlying mechanism.

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“…Although detrimental in nature, but few studies of their beneficial effects have been reported. ROS appeared to play an important role in proapoptotic pathway in Cutaneous T-cell lymphoma (CTCL) when treated with the indirubin derivative DKP-071 ( Soltan et al., 2019 ). In a search for newer antitumor strategy, a sharp decrease in cell proliferation and cell viability was observed with DKP-071.…”

Section: Introductionmentioning

confidence: 99%

The role of Safranal and saffron stigma extracts in oxidative stress, diseases and photoaging: A systematic review

Nanda

Madan

2021

Heliyon

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Reactive oxygen species (ROS) are produced as a result of various environmental factors and cellular metabolism reactions creating oxidative stress. The reversible oxidative modification on proteins such as cysteine oxidation may be useful and can play positive role. ROS generated offer some benefits such as cellular signalling and tissue repair when present in low concentration. However, most of the times, these reactive species cause detrimental effects to cell components which leads to various pathological conditions which causes or aggravates diseases due to oxidative stress. The degenerative diseases due to oxidative stress are diabetes, cardiovascular diseases, epilepsy, cancer and aging. Antioxidants are the compounds which scavenge these free radicals and hence neutralize their effects. Research has enabled the use of natural antioxidants as therapeutic agent in the treatment of diseases. Safranal is one such natural agent which is a major volatile component of saffron. Saffron, Red gold is the most expensive spice found in limited region of the planet and is also reported to be used in traditional systems of medicine. Chemically, safranal is a monoterpene aldehyde possessing a sweet fragrance. While exploring for the photoprotective properties of safranal, we learnt about the immense antioxidant potential of safranal. Investigation by various research groups established safranal as an anti-inflammatory, antidepressant, anxiolytic, antiasthamatic, antihypertensive, anticonvulsant, anticancer and antitussive and antigenotoxic agent. It has brought researchers over the world to explore the antioxidant benefits of saffron for human health. In the present paper, potential of safranal and its related molecules as radical scavenger in combating oxidative stress, diseased conditions is collated and the underlying mechanisms have been explained. Various cell lines and animal models used for study of Safranal have been discussed.

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Key Role of Reactive Oxygen Species (ROS) in Indirubin Derivative-Induced Cell Death in Cutaneous T-Cell Lymphoma Cells

Cited by 19 publications

References 45 publications

Countering TRAIL Resistance in Melanoma

Countering TRAIL Resistance in Melanoma

Evaluation of the Developmental Toxicity Induced by E804 in Zebrafish Embryos

The role of Safranal and saffron stigma extracts in oxidative stress, diseases and photoaging: A systematic review

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