Transcriptome Changes in Colorectal Cancer Cells upon Treatment with Avicequinone B
Autor: | David E. Rivera, Luis A. Franco, Yanet Ocampo, Jhoan Piermattey, Daneiva Caro, Ricardo Gaitan |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Programmed cell death
RNA-sequencing Pharmaceutical Science 02 engineering and technology Biology 030226 pharmacology & pharmacy Transcriptome 03 medical and health sciences 0302 clinical medicine Interferon medicine Cytotoxic T cell Ferroptosis MTT assay General Pharmacology Toxicology and Pharmaceutics lcsh:RM1-950 Interferon stimulated genes 021001 nanoscience & nanotechnology medicine.disease Colorectal cancer lcsh:Therapeutics. Pharmacology Avicequinone B Apoptosis Cancer cell Cancer research Adenocarcinoma miR-21 0210 nano-technology medicine.drug Research Article |
Zdroj: | Advanced Pharmaceutical Bulletin Advanced Pharmaceutical Bulletin, Vol 10, Iss 4, Pp 638-647 (2020) |
ISSN: | 2251-7308 2228-5881 |
Popis: | Purpose: Naphtho[2,3-b]furan-4,9-dione (Avicequinone B), a natural naphthoquinone isolated from the mangrove tree Avicennia alba, is recognized as a valuable synthetic precursor with anti-proliferative effect. However, the molecular mechanism involved in its bioactivity has not been investigated. This study aimed to determine the selectivity of avicequinone B against cancer cells and the transcriptomic changes induced in colorectal cancer (CRC). Methods: The cytotoxic effect against adenocarcinoma-derived cells or fibroblasts was evaluated using MTT assay. In addition, CRC cells were treated with avicequinone B in different settings to evaluate colony-forming ability, cell cycle progression, apoptosis/necrosis induction, and transcriptome response by RNA-seq. Results: Avicequinone B effectively reduced the viability of breast, colorectal, and lung adenocarcinoma cells with IC50 lower than 10 μM, while fibroblasts were less affected. The induction of G2/M arrest and necrosis-like cell death were observed in avicequinone B-treated HT-29 cells. Furthermore, RNA-seq revealed 490 differentially expressed genes, highlighting the reduction of interferon stimulated genes and proliferative signaling pathways (JAK-STAT, MAPK, and PI3K-AKT), as well as the induction of ferroptosis and miR-21 expression. Conclusion: In short, these results demonstrated the therapeutic potential of avicequinone B and paved the foundation for elucidating its mechanisms in the context of CRC. |
Databáze: | OpenAIRE |
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