Home Life Sciences Diselenide-derivative of 3-pyridinol targets redox enzymes leading to cell cycle deregulation and apoptosis in A549 cells
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Diselenide-derivative of 3-pyridinol targets redox enzymes leading to cell cycle deregulation and apoptosis in A549 cells

  • Vishwa V. Gandhi , Subhash C. Bihani , Prasad P. Phadnis and Amit Kunwar ORCID logo EMAIL logo
Published/Copyright: August 25, 2022
Biological Chemistry
From the journal Biological Chemistry Volume 403 Issue 10

Abstract

The aim of present study was to understand the mechanism of action of 2,2′-diselenobis(3-pyridinol) or DISPOL in human lung cancer (A549) cells. A549 cells were treated with 10 µM (∼IC50) of DISPOL for varying time points to corelate the intracellular redox changes with its cytotoxic effect. The results indicated that DISPOL treatment led to a time dependant decrease in the basal level of reactive oxygen species (ROS). Additionally, DISPOL treatment elevated the ratio of reduced (GSH) and oxidised (GSSG) glutathione by upregulating gamma-glutamylcysteine ligase (γ-GCL) involved in GSH biosynthesis and inhibiting the activities of redox enzymes responsible for GSH utilization and recycling, such as glutathione-S-transferase (GST) and glutathione reductase (GR). Molecular docking analysis suggests putative interactions of DISPOL with GST and GR which could account for its inhibitory effect on these enzymes. Further, DISPOL induced reductive environment preceded G1 arrest and apoptosis as evidenced by decreased expression of cell cycle genes (Cyclin D1 and Cyclin E1) and elevation of p21 and apoptotic markers (cleaved caspase 3 and cleaved PARP). The combinatorial experiments involving DISPOL and redox modulatory agents such as N-acetylcysteine (NAC) and buthionine sulfoximine (BSO) indeed confirmed the role of reductive stress in DISPOL-induced cell death. Finally, Lipinski’s rule suggests attributes of drug likeness in DISPOL. Taken together, DISPOL exhibits a novel mechanism of reductive stress-mediated cell death in A549 cells that warrants future exploration as anticancer agent.

Keywords: apoptosis; cell cycle arrest; organodiselenides; reactive oxygen species; redox modulation
Corresponding author: Amit Kunwar, Radiation and Photochemistry Division, Bhabha Atomic Research Centre, Mumbai 400085, India; and Homi Bhabha National Institute, Anushaktinagar, Mumbai 400094, India, E-mail:

Acknowledgments

The authors acknowledge Dr. Awadhesh Kumar, Head, RPC Division BARC and Dr. A. K. Tyagi, Associate Director, Chemistry Group, BARC for their support and encouragement.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Conflict of interest statement: The authors declare no conflicts of interest regarding this article.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/hsz-2022-0123).

Received: 2022-02-18
Accepted: 2022-08-01
Published Online: 2022-08-25
Published in Print: 2022-09-27

© 2022 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Research Articles/Short Communications
  3. Cell Biology and Signaling
  4. Diselenide-derivative of 3-pyridinol targets redox enzymes leading to cell cycle deregulation and apoptosis in A549 cells
  5. NF90/NFAR (nuclear factors associated with dsRNA) – a new methylation substrate of the PRMT5-WD45-RioK1 complex
  6. PHF20L1 mediates PAX2 expression to promote angiogenesis and liver metastasis in colorectal cancer through regulating HIC1
  7. Nitazoxanide inhibits osteosarcoma cells growth and metastasis by suppressing AKT/mTOR and Wnt/β-catenin signaling pathways
  8. LncRNA-p21 suppresses cell proliferation and induces apoptosis in gastric cancer by sponging miR-514b-3p and up-regulating ARHGEF9 expression
  9. L-theanine induces skeletal muscle fiber type transformation by activation of prox1/CaN signaling pathway in C2C12 myotubes
  10. Proteolysis
  11. TMPRSS13 zymogen activation, surface localization, and shedding is regulated by proteolytic cleavage within the non-catalytic stem region
https://doi.org/10.1515/hsz-2022-0123
Keywords for this article
apoptosis; cell cycle arrest; organodiselenides; reactive oxygen species; redox modulation

Articles in the same Issue

  1. Frontmatter
  2. Research Articles/Short Communications
  3. Cell Biology and Signaling
  4. Diselenide-derivative of 3-pyridinol targets redox enzymes leading to cell cycle deregulation and apoptosis in A549 cells
  5. NF90/NFAR (nuclear factors associated with dsRNA) – a new methylation substrate of the PRMT5-WD45-RioK1 complex
  6. PHF20L1 mediates PAX2 expression to promote angiogenesis and liver metastasis in colorectal cancer through regulating HIC1
  7. Nitazoxanide inhibits osteosarcoma cells growth and metastasis by suppressing AKT/mTOR and Wnt/β-catenin signaling pathways
  8. LncRNA-p21 suppresses cell proliferation and induces apoptosis in gastric cancer by sponging miR-514b-3p and up-regulating ARHGEF9 expression
  9. L-theanine induces skeletal muscle fiber type transformation by activation of prox1/CaN signaling pathway in C2C12 myotubes
  10. Proteolysis
  11. TMPRSS13 zymogen activation, surface localization, and shedding is regulated by proteolytic cleavage within the non-catalytic stem region
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