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AMTAC-19, a Spiro-Acridine Compound, Induces In Vitro Antitumor Effect via the ROS-ERK/JNK Signaling Pathway. | LitMetric

AI Article Synopsis

  • - Colorectal cancer remains a major global health issue, and the compound AMTAC-19 has demonstrated significant cytotoxicity against HCT-116 colorectal cancer cells, with an IC50 value of 10.35 ± 1.66 µM, along with antioxidant effects after 48 hours of treatment.
  • - The study utilized Molegro Virtual Docker software to analyze how AMTAC-19 interacts with key signaling proteins (ERK1, JNK1, and p38α MAPK) and conducted various in vitro assays to assess its effects on these pathways in HCT-116 cells.
  • - Results showed that AMTAC-19 activates ERK1/2 and JNK1, increases reactive

Article Abstract

Colorectal cancer remains a significant cause of mortality worldwide. A spiro-acridine derivative, ()-1'-((4-bromobenzylidene)amino)-5'-oxo-1',5'-dihydro-10-spiro[acridine-9,2'-pyrrole]-4'-carbonitrile (AMTAC-19), showed significant cytotoxicity in HCT-116 colorectal carcinoma cells (half maximal inhibitory concentration, IC50 = 10.35 ± 1.66 µM) and antioxidant effects after 48 h of treatment. In this study, Molegro Virtual Docker v.6.0.1 software was used to investigate the interactions between AMTAC-19 and the Extracellular Signal-Regulated Kinase 1 (ERK1), c-Jun N-terminal Kinase 1 (JNK1), and p38 Mitogen-Activated Protein Kinase α (p38α MAPK). In vitro assays were conducted in HCT-116 cells to evaluate the effect of AMTAC-19 on the modulation of these proteins' activities using flow cytometry. Furthermore, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in the presence or absence of ERK1/2, JNK, and p38 MAPK inhibitors was used to evaluate the involvement of these enzymes in AMTAC-19 cytotoxicity. ROS production was assessed using the 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA) assay at various incubation times (30 min, 1 h, 6 h, 12 h, and 24 h), and the MTT assay using N-acetyl-L-cysteine (NAC) was performed. In silico results indicated that AMTAC-19 interacts with ERK1, JNK1, and p38α MAPK. Additionally, AMTAC-19 activated ERK1/2 and JNK1 in HCT-116 cells, and its cytotoxicity was significantly reduced in the presence of ERK1/2 and JNK inhibitors. AMTAC-19 also induced a significant increase in ROS production (30 min and 1 h), while NAC pretreatment reduced its cytotoxicity. These findings support AMTAC-19's in vitro antitumor effect through ROS-dependent activation of ERK and JNK pathways.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11596224PMC
http://dx.doi.org/10.3390/molecules29225344DOI Listing

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