2,2′-Dipyridyl diselenide (<b>Py2Se2</b>) induces G1 arrest and apoptosis in human lung carcinoma (A549) cells through ROS scavenging and reductive stress

Gandhi, Vishwa V.; Phadnis, Prasad P.; Kunwar, Amit

doi:10.1039/d0mt00106f

Cited by 14 publications

(13 citation statements)

References 53 publications

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“…Thus together these results have suggested that Py2Se2 or Nic2Se2 induces reductive environment in cells. However, the extent of reductive state in terms of the fold change in the ratio of GSH/GSSG was significantly higher in Py2Se2 treated cells as compared toNic2Se2 treated cells [10,11]. Further reductive stress in Py2Se2 treated A549 cells were found to be associated with DNA damage, G1 phase arrest and apoptosis [11].…”

Section: Comparative Cytotoxicity and Redox Modulation In Cellsmentioning

confidence: 89%

“…Alternatively; the test compound can also be evaluated for its competitive inhibitory effect on TrxR mediated reduction of DTNB (dithionitrobenzoic acid) into TNB (thionitrobenzoic acid). Interestingly, at an equimolar concentration, both Nic2Se2 and Py2Se2 have been found to increase the decay of NADPH or to inhibit TNB formation in TrxR activity assay reactions suggesting that these molecules can undergo TrxR mediated reduction [10,11]. Notably Nic2Se2 appeared to be more potent substrate than Py2Se2 for the mammalian TrxR (Figure 1).…”

Section: Substrate Of Trxrmentioning

confidence: 97%

“…However, results have shown that treatment of CHO and A549 cells with Nic2Se2 and Py2Se2 respectively in the nearly identical concentration range (10-25 µ M) resulted in a significant decrease in basal ROS level and a concurrent increase in total thiol content as well as increase in the ratio of glutathione couple (GSH/GSSH) (Figure 2) [10,11]. Additionally, treatment with Py2Se2 or Nic2Se2 led to significant increase in the transcript level of γ-GCL, a rate limiting enzyme involved in GSH biosynthesis [10,11]. Thus together these results have suggested that Py2Se2 or Nic2Se2 induces reductive environment in cells.…”

Section: Comparative Cytotoxicity and Redox Modulation In Cellsmentioning

confidence: 99%

“…Several studies have shown that TrxR can reduce the organodiselenides in to corresponding selenols and/or selone [3,4,[10][11][12]. Accordingly, Nic2Se2 and Py2Se2 have been evaluated for their ability to undergo TrxR mediated reduction.…”

Section: Substrate Of Trxrmentioning

confidence: 99%

“…Having understood the catalytic activities of Py2Se2 andNic2Se2, these molecules have been investigated for cytotoxicity in cellular models [7,8,10,11]. The Table 1 shows the IC50 values of Py2Se2 and Nic2Se2 to induce cytotoxicity in various cell types by MTT assay.…”

Section: Comparative Cytotoxicity and Redox Modulation In Cellsmentioning

confidence: 99%

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Paradoxical Behavior of Organodiselenides: Pro-Oxidant to Antioxidant

Kunwar

2020

The 1st International Electronic Conference on Catalysis Sciences

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Over the years, organodiselenides have emerged as the biologically relevant class of molecules. On one hand, such compounds are known for pro-oxidant effects leading to toxicity in biological systems. On the other hand, there are growing evidences about their bio-mimetic activities as catalysts such as glutathione peroxidase (GPx)-like activity. Our recent work has explored this paradoxical behavior of diselenides in developing antioxidants and/or anticancer agents. For this, a number of alkyl and aryldiselenides have been evaluated in different biological models. The results have shown that aryl diselenides specifically pyridinediselenides alter the ratio of the intracellular thiol redox pairs (GSH and GSSG) towards reduction (antioxidant) rather than oxidation(pro-oxidant) to protect normal cells against radiation damage as well asto induce cytotoxicity in tumor cells. Further, these studies have also postulated that intracellular redox state, level of thioredoxin reductase (TrxR) and reductive intermediates (like selenol and/or selone) might play a very important role in the manifestation of the toxicities of aryl diselenides in cells

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Section: Comparative Cytotoxicity and Redox Modulation In Cellsmentioning

confidence: 89%

Section: Substrate Of Trxrmentioning

confidence: 97%

Section: Comparative Cytotoxicity and Redox Modulation In Cellsmentioning

confidence: 99%

Section: Substrate Of Trxrmentioning

confidence: 99%

Section: Comparative Cytotoxicity and Redox Modulation In Cellsmentioning

confidence: 99%

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Paradoxical Behavior of Organodiselenides: Pro-Oxidant to Antioxidant

Kunwar

2020

The 1st International Electronic Conference on Catalysis Sciences

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Nanomaterials‐Induced Redox Imbalance: Challenged and Opportunities for Nanomaterials in Cancer Therapy

Wu,

Zhou,

et al. 2024

Advanced Science

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Cancer cells typically display redox imbalance compared with normal cells due to increased metabolic rate, accumulated mitochondrial dysfunction, elevated cell signaling, and accelerated peroxisomal activities. This redox imbalance may regulate gene expression, alter protein stability, and modulate existing cellular programs, resulting in inefficient treatment modalities. Therapeutic strategies targeting intra‐ or extracellular redox states of cancer cells at varying state of progression may trigger programmed cell death if exceeded a certain threshold, enabling therapeutic selectivity and overcoming cancer resistance to radiotherapy and chemotherapy. Nanotechnology provides new opportunities for modulating redox state in cancer cells due to their excellent designability and high reactivity. Various nanomaterials are widely researched to enhance highly reactive substances (free radicals) production, disrupt the endogenous antioxidant defense systems, or both. Here, the physiological features of redox imbalance in cancer cells are described and the challenges in modulating redox state in cancer cells are illustrated. Then, nanomaterials that regulate redox imbalance are classified and elaborated upon based on their ability to target redox regulations. Finally, the future perspectives in this field are proposed. It is hoped this review provides guidance for the design of nanomaterials‐based approaches involving modulating intra‐ or extracellular redox states for cancer therapy, especially for cancers resistant to radiotherapy or chemotherapy, etc.

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Antitumor Activity and Reductive Stress by Platinum(II) N‐Heterocyclic Carbenes based on Guanosine**

Leitão

Turos-Cabal

Sánchez‐Sánchez

et al. 2023

Chemistry A European J

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Platinum(II) complexes bearing N-heterocyclic carbenes based guanosine and caffeine have been synthesized by unassisted CÀ H oxidative addition, leading to the corresponding trans-hydride complexes. Platinum guanosine derivatives bearing triflate as counterion or bromide instead of hydride as co-ligand were also synthesized to facilitate correlation between structure and activity. The hydride compounds show high antiproliferative activity against all cell lines (TC-71, MV-4-11, U-937 and A-172). Methyl Guanosine complex 3, bearing a hydride ligand, is up to 30 times more active than compound 4, with a bromide in the same position. Changing the counterion has no significant effect in antiproliferative activity. Increasing bulkiness at N7, with an isopropyl group (compound 6), allows to maintain the antiproliferative activity while decreasing toxicity for noncancer cells. Compound 6 leads to an increase in endoplasmic reticulum and autophagy markers on TC71 and MV-4-11 cancer cells, induces reductive stress and increases glutathione levels in cancer cells but not in non-cancer cell line HEK-293.

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2,2′-Dipyridyl diselenide (Py2Se2) induces G1 arrest and apoptosis in human lung carcinoma (A549) cells through ROS scavenging and reductive stress

Abstract: This study demonstrates the cytotoxic activity and the underlying mechanisms of a synthetic organoselenium compound containing pyridine and diselenide moieties.

Cited by 14 publications

References 53 publications

Paradoxical Behavior of Organodiselenides: Pro-Oxidant to Antioxidant

Paradoxical Behavior of Organodiselenides: Pro-Oxidant to Antioxidant

Nanomaterials‐Induced Redox Imbalance: Challenged and Opportunities for Nanomaterials in Cancer Therapy

Antitumor Activity and Reductive Stress by Platinum(II) N‐Heterocyclic Carbenes based on Guanosine**

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