Pharmaceuticals (Nov 2023)

The Essential Oil from <i>Conyza bonariensis</i> (L.) Cronquist (Asteraceae) Exerts an In Vitro Antimelanoma Effect by Inducing Apoptosis and Modulating the MAPKs, NF-κB, and PKB/AKT Signaling Pathways

  • Rafael Carlos Ferreira,
  • Sâmia Sousa Duarte,
  • Valgrícia Matias de Sousa,
  • Ramon Ramos Marques de Souza,
  • Karinne Kelly Gadelha Marques,
  • Renata Albuquerque de Abrantes,
  • Yuri Mangueira do Nascimento,
  • Natália Ferreira de Sousa,
  • Marcus Tullius Scotti,
  • Luciana Scotti,
  • Josean Fechine Tavares,
  • Juan Carlos Ramos Gonçalves,
  • Marcelo Sobral da Silva,
  • Marianna Vieira Sobral

DOI
https://doi.org/10.3390/ph16111553
Journal volume & issue
Vol. 16, no. 11
p. 1553

Abstract

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The characterization and cytotoxicity of the essential oil from Conyza bonariensis (L.) aerial parts (CBEO) were previously conducted. The major compound was (Z)-2-lachnophyllum ester (EZ), and CBEO exhibited significant ROS-dependent cytotoxicity in the melanoma cell line SK-MEL-28. Herein, we employed the Molegro Virtual Docker v.6.0.1 software to investigate the interactions between the EZ and Mitogen-Activated Protein Kinases (MAPKs), the Nuclear Factor kappa B (NF-κB), and the Protein Kinase B (PKB/AKT). Additionally, in vitro assays were performed in SK-MEL-28 cells to assess the effect of CBEO on the cell cycle, apoptosis, and these signaling pathways by flow cytometry and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using MAPKs inhibitors. CBEO induced a significant increase in the sub-G1 peak, as well as biochemical and morphological changes characteristic of apoptosis. The in-silico results indicated that EZ interacts with Extracellular Signal-Regulated Kinase 1 (ERK1), c-Jun N-terminal Kinase 1 (JNK1), p38α MAPK, NF-κB, and PKB/AKT. Moreover, CBEO modulated the ERK1/2, JNK, p38 MAPK, NF-κB, and PKB/AKT activities in SK-MEL-28 cells. Furthermore, CBEO’s cytotoxicity against SK-MEL-28 cells was significantly altered in the presence of MAPKs inhibitors. These findings support the in vitro antimelanoma effect of CBEO through apoptosis induction, and the modulation of ERK, JNK, p38 MAPK, NF-κB, and PKB/AKT activities.

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