Sensitization of cancer cells to radiation by selenadiazole derivatives by regulation of ROS-mediated DNA damage and ERK and AKT pathways

Xie, Qiang; Zhou, Yangliang; Lan, Guoqiang; Yang, Li‐Ye; Zheng, Wenjie; Liang, Yuanwei; Chen, Tianfeng

doi:10.1016/j.bbrc.2014.04.151

Cited by 52 publications

(36 citation statements)

References 24 publications

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“…In this study, Akt, JNK, ERK1/2, and p38 were regulated by PSVII in K562/ADR cells, suggesting that the Akt/MAPK pathway was a potential target of PSVII. Previous studies have suggested a close link between ROS generation and the modulation of MDR transporters, including P‐gp and MRPs (Felix & Barrand, ; Joshi et al, ; Xie et al, ). Several reports have indicated a negative correlation between ROS production and MDR transporter expression by showing that increased intracellular ROS levels lead to the downregulation of intrinsic P‐gp expression.…”

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 98%

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Paris saponin VII induces cell cycle arrest and apoptosis by regulating Akt/MAPK pathway and inhibition of P‐glycoprotein in K562/ADR cells

Yan

Wang

et al. 2018

Phytotherapy Research

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Paris saponinVII (PSVII) is a steroidal saponin isolated from the roots and rhizomes of Trillium tschonoskii Maxim. We found that PSVII could inhibit the growth of adriamycin-resistant human leukemia cells (K562/ADR) in a dose-dependent manner. Furthermore, the molecular mechanism underlying the cytotoxicity and downregulation of P-glycoprotein (P-gp) expression by PSVII was clarified. PSVII significantly suppressed cell proliferation by cell cycle arrest in the G0/G1 phase, which was associated with an obvious decrease in cyclin B1/D1 and CDK2/4/6 protein expression. Moreover, PSVII could attenuate mitochondrial membrane potential, increase the expression of apoptosis-related proteins, such as Bax and cytochrome c, and decrease the protein expression levels of Bcl-2, caspase-9, caspase-3, PARP-1, and p-Akt. We also found that JNK, ERK1/2, and p38 were regulated by PSVII in K562/ADR cells. And further studies indicated that the decrease in the reactive oxygen species level inhibited intrinsic P-gp expression. Therefore, PSVII-induced apoptosis in K562/ADR cells was associated with Akt/MAPK and the inhibition of P-gp. In addition, PSVII induced a robust autophagy in K562/ADR cells as demonstrated by the degradation of LC3-I. These results provide a biochemical basis for possible clinical applications of PSVII in the treatment of leukemia.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 98%

Paris saponin VII induces cell cycle arrest and apoptosis by regulating Akt/MAPK pathway and inhibition of P‐glycoprotein in K562/ADR cells

Yan

Wang

et al. 2018

Phytotherapy Research

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“…In contrast, a marked decrease of TrxR activity (65.8%) was observed in cells cooperatively treated with 283 (5 μM) and radiation (8 Gy). They demonstrated that inhibition of TrxR contributed to the synergism effect between 283 and radiation, which led to a growth inhibition of cancer cells . In addition, the binding site of the enzyme with 1, 2, 5‐selenadiazole ( 284 , Figure ) was studied by MALDI‐TOF MS using a model peptide of TrxR.…”

Section: Thioredoxin Reductase Inhibitorsmentioning

confidence: 99%

Small molecule inhibitors of mammalian thioredoxin reductase as potential anticancer agents: An update

Zhang

et al. 2018

Medicinal Research Reviews

135

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Mammalian thioredoxin reductase (TrxR) enzymes are homodimeric flavin proteins sharing a unique yet essential selenocysteine residue at their C-terminus. TrxRs, together with their endogenous substrate thioredoxins, play a crucial role in regulating diverse cellular redox events. A wealth of evidence from both clinic observations and bench studies supports that overactivation/dysfunction of TrxRs has a close link to the onset and development of various diseases, such as cancer and neurodegeneration. Thus, an increasing interest has been attracted to find small molecule modulators of TrxRs during the past years. Herein, we briefly discussed the relevance of targeting TrxRs inhibition for cancer treatment, and presented the small molecule inhibitors of mammalian TrxRs published in the nonpatent literatures from 2011 to 2016. The mechanisms of inhibition by different classes of molecules were summarized, and some inhibitors with promising anticancer activity were further discussed. We expect this work would be a comprehensive reference in the medicinal chemistry, and have a broad audience across multiple disciplines.

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“…(ROS)-mediated DNA damage, the extracellular signal-regulated kinase (ERK) and protein kinase B( AKT) pathways, [18] inhibiting thioredoxin reductase (TrxR) to disruptc ellular redox balance, ando vercoming hyperglycemia-induced drug resistance. [19,20] These reports demonstrate their potentiali nc ancer therapy.…”

Section: Introductionmentioning

confidence: 99%

Microwave‐Assisted Syntheses of Benzimidazole‐Containing Selenadiazole Derivatives That Induce Cell‐Cycle Arrest and Apoptosis in Human Breast Cancer Cells by Activation of the ROS/AKT Pathway

et al. 2016

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The use of selenium-containing heterocyclic compounds as potent cancer chemopreventive and chemotherapeutic agents has been well documented by a large number of clinical studies. In this study we developed a new approach to synthesize four benzimidazole-containing selenadiazole derivatives (BSeDs). The method uses a combination of peptide coupling reagents and microwave irradiation. This strategy features milder reaction conditions, higher yields, and shorter reaction times. The synthetic BSeDs were identified as potent antiproliferative agents against the human MCF-7 and MDA-MB-231 breast cancer cell lines. Compounds 1 b (5-(6-methyl-1H-benzo[d]imidazol-2-yl)benzo[c][1,2,5]selenadiazole), 1 c (5-(6-chloro-1H-benzo[d]imidazol-2-yl)benzo[c][1,2,5]selenadiazole), and 1 d (5-(6-bromo-1H-benzo[d]imidazol-2-yl)benzo[c][1,2,5]selenadiazole) were found to show greater cytotoxicity against the triple-negative breast cancer cell line MDA-MB-231 than MCF-7, and to exhibit dose-dependent inhibition of cell migration, in which a significant decrease in the zone of cell monolayer wound closure was observed relative to untreated controls. Our results demonstrate that BSeDs can cause cell-cycle arrest and apoptosis in MDA-MB-231 cells by inducing DNA damage, inhibiting protein kinase B (AKT), and activating mitogen-activated protein kinase (MAPK) family members through the overproduction of reactive oxygen species (ROS). Taken together, the results of this study provide a facile microwave-assisted strategy for the synthesis of selenium-containing organic compounds that exhibit a high level of anticancer efficacy.

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Sensitization of cancer cells to radiation by selenadiazole derivatives by regulation of ROS-mediated DNA damage and ERK and AKT pathways

Cited by 52 publications

References 24 publications

Paris saponin VII induces cell cycle arrest and apoptosis by regulating Akt/MAPK pathway and inhibition of P‐glycoprotein in K562/ADR cells

Paris saponin VII induces cell cycle arrest and apoptosis by regulating Akt/MAPK pathway and inhibition of P‐glycoprotein in K562/ADR cells

Small molecule inhibitors of mammalian thioredoxin reductase as potential anticancer agents: An update

Microwave‐Assisted Syntheses of Benzimidazole‐Containing Selenadiazole Derivatives That Induce Cell‐Cycle Arrest and Apoptosis in Human Breast Cancer Cells by Activation of the ROS/AKT Pathway

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