Transcriptome Changes in Colorectal Cancer Cells upon Treatment with Avicequinone B

Abstract

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.

Ferroptosis‐modulating small molecules for targeting drug‐resistant cancer: Challenges and opportunities in manipulating redox signaling

“…The naphthoquinone 119 (Figure 13 ) from the mangrove tree Avicennia alba reduced the viability of human breast, colorectal, and lung adenocarcinoma cells (EC 50 = 3–12 µM). 389 Transcriptome analysis revealed that 119 regulates ferroptosis‐related genes (e.g., SLC7A11 and GCL), however, in the opposite direction as expected for ferroptosis induction. The authors speculate about unknown targets and feedback mechanisms.…”

“…The authors speculate about unknown targets and feedback mechanisms. 389 9.4.10 | Gallic acid (120) 3,4,5-Trihydroxybenzoic acid (120; Figure 13) is prevalent in Quercus species and has recently been proposed to induce ferroptosis besides apoptosis and necroptosis at high concentrations (300 µM) in human HeLa epithelial adenocarcinoma cells, H446 lung carcinoma epithelial cells, SH-SY5Y neuroblastoma cells, MDA-MB-231 breast cancer cells and A375 melanoma cancer cells. 390,391 The contribution of ferroptosis to cell death induction remains enigmatic.…”

“…Transcriptome analysis revealed that 119 regulates ferroptosis‐related genes (e.g., SLC7A11 and GCL), however, in the opposite direction as expected for ferroptosis induction. The authors speculate about unknown targets and feedback mechanisms 389 …”

Biologically Active Plant-Derived Substances With Antimicrobial Properties

“…Modern research into the medicinal effects of plant substances uses the latest technologies and analytical techniques, and the traditional use of medicinal plants is supported by multidirectional scientific research. New substances present in raw plants are constantly being discovered, which may be of importance in medicine because of their great potential to destroy microorganisms or because of their antioxidant and anticancer properties [30].…”