Tabriz University of Medical Sciences Advanced Pharmaceutical Bulletin 2228-5881 10 4 2020 08 09 Transcriptome Changes in Colorectal Cancer Cells upon Treatment with Avicequinone B 638 647 10.34172/apb.2020.077 EN Yanet Ocampo https://orcid.org/0000-0003-2001-3848 Daneiva Caro https://orcid.org/0000-0001-8079-5664 David Rivera Jhoan Piermattey Ricardo Gaitán Luis A. Franco https://orcid.org/0000-0003-2983-0836 Journal Article 10.34172/apb.2020.077 2019 10 22 2020 01 27 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.