Cell Cycle Regulation and Apoptotic Cell Death in Experimental Colon Carcinogenesis: Intervening with Cyclooxygenase-2 Inhibitors
Abstract
Relative imbalance in the pathways regulating cell cycle, cell proliferation, or cell death marks a prerequisite for neoplasm. C-phycocyanin, a biliprotein from Spirulina platensis and a selective COX-2 inhibitor along with piroxicam, a traditional nonsteroidal antiinflammatory drug was used to investigate the role of cell cycle regulatory proteins and proinflammatory transcription factor NFκB in 1,2-dimethylhydrazine dihydrochloride (DMH)-induced rat colon carcinogenesis. Cell cycle regulators [cyclin D1, cyclin E, cyclin dependent kinase 2 (CDK2), CDK4, and p53], NFκB (p65) pathway, and proliferating cell nuclear antigen (PCNA) were evaluated by gene and protein expression, whereas apoptosis was studied by terminal deoxynucleotidyl transferase dUTP nick end labeling and apoptotic bleb assay. Molecular docking of ligand protein interaction was done to validate the in vivo results. Cyclin D1, cyclin E, CDK2, and CDK4 were overexpressed in DMH, whereas piroxicam and c-phycocyanin promoted the cell cycle arrest by downregulating them. Both drugs mediated apoptosis through p53 activation. Piroxicam and c-phycocyanin also stimulated antiproliferation by restraining PCNA expression and reduced cell survival via inhibiting NFκB (p65) pathway. Molecular docking revealed that phycocyanobilin (a chromophore of c-phycocyanin) interact with DNA binding site of NFκB. Inhibition of cyclin/CDK complex by piroxicam and c-phycocyanin affects the expression of p53 in colon cancer followed by downregulation of NFκB and PCNA levels, thus substantiating the antineoplastic role of these agents.
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C-phycocyanin inhibits NF-kB and induces Nrf2 activation in pancreatic β-cell INS-1.
“In particular, C-phycocyanin was able to inhibit NF-kB [54] and induced Nrf2 activation in pancreatic β-cell INS-1 [55].”
From Antioxidant, Immunomodulating, and Microbial‐Modulating Activities of the Sustainable and Ecofriendly <i>Spirulina</i> (2017) · cites this paper as [54]
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- Authors
- Saini, M. K., & Sanyal, S. N.
- Affiliations
- Panjab University (IN)
- Corresponding author
- Sanyal, Sankar Nath
- ORCID
- Saini, Manpreet Kaur
- Venue
- Nutrition and Cancer
- Publisher
- Informa UK Limited
- Published
- 2015-03-31
- Volume
- 67
- Issue
- 4
- Pages
- 620-636
- ISSN
- 0163-5581 (ISSN-L)
- 1532-7914
- OpenAlex
- W2038478175
- Cited by
- 37
- References
- 50
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 5 · 2023: 2 · 2022: 7 · 2021: 6 · 2020: 2 · 2018: 2 · 2017: 5 · 2016: 4
- FWCI
- 2.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nutrition and Cancer (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Physical Sciences › Chemistry › Organic Chemistry › Synthesis and biological activity
- Keywords
- colon carcinogenesis, COX-2 inhibitors, C-phycocyanin, piroxicam, 1,2-dimethylhydrazine, cell cycle regulation, apoptosis, NF-κB, p53, cyclin D1, cyclin E, cyclin-dependent kinases, proliferating cell nuclear antigen, phycocyanobilin, Spirulina platensis, DNA binding, anticancer agents
- MeSH terms
- Animals, Anti-Inflammatory Agents, Non-Steroidal, Antineoplastic Agents, Colon, Colonic Neoplasms, DNA-Binding Proteins, Male, Phycocyanin, Piroxicam, Signal Transduction, Tumor Suppressor Protein p53, NF-kappa B, Rats, Sprague-Dawley, Apoptosis, 1,2-Dimethylhydrazine, Cyclin E, Cyclin D1, Cell Proliferation, Cyclin-Dependent Kinase 2, Cyclin-Dependent Kinase 4, Rats, Cyclooxygenase 2 Inhibitors, Phycobilins, Cell Cycle Checkpoints, Carcinogenesis
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