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Peer-reviewedCC BYACS omega

Signaling Pathways Mediating the Cytotoxicity of (E)-4-(1-Epoxy-7,8-propenyl)phenyl Benzoate, a Phenylpropanoid from Croton velutinus, in MCF‑7 Cells

  • Renata A. de Abrantes1
  • Sâmia S. Duarte1
  • Rafael C. Ferreira1
  • Ana Paula G. M. Farias1
  • Geraldo M. W. Amorim1
  • Paulo B. A. Loureiro1
  • Ramon R. M. de Souza1
  • Valgrícia M. de Sousa1
  • Gabriela B. de Lyra1
  • Isabela C. F. Silva1
  • Lucas S. Abreu2
  • Eudes da S. Velozo3
4 more authors
  • Juan C. R. Gonçalves1
  • Marcelo S. da Silva1
  • Josean F. Tavares1
  • Marianna V. Sobral1
  1. 1Federal University of Paraíba (UFPB) , , , ,
  2. 2Fluminense Federal University , , , ,
  3. 3Federal University of Bahia , , , ,
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Abstract

Natural products represent an important source of candidates for breast cancer therapy. Here, we investigated the antitumor activity of (E)-4-(1-epoxy-7,8-propen)phenylbenzoate (CV2), a phenylpropanoid isolated from Croton velutinus roots, in MCF-7 breast cancer cells and evaluated its toxicity profile in nontumor cells and zebrafish embryos. CV2 exhibited potent cytotoxic activity against MCF-7 cells (IC50= 4.63 ± 0.16 μM) and showed selectivity relative to nontumorigenic MCF-10A cells (SI = 9.69). CV2 also induced apoptosis, increased intracellular ROS levels, and modulated MAPK, NF-κB, and PKB/AKT signaling pathways. Pretreatment with N-acetylcysteine or MAPK inhibitors significantly attenuated CV2-induced cytotoxicity, supporting the involvement of oxidative stress and MAPK signaling in its biological effects. In toxicity studies, CV2 exhibited cytotoxicity toward peripheral blood mononuclear cells (PBMCs; IC50 = 1.75 ± 0.06 μM) and an LC50 of 3.07 μM in zebrafish embryos, accompanied by alterations in oxidative stress-related enzymes. Collectively, these findings demonstrate that CV2 possesses significant antitumor activity against breast cancer cells while highlighting the need for further studies to better define its safety profile and therapeutic potential.

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Cite

BibTeXRIS
BibTeX
@article{abrantes2026signaling,
  title = {{Signaling Pathways Mediating the Cytotoxicity of (E)-4-(1-Epoxy-7,8-propenyl)phenyl Benzoate, a Phenylpropanoid from Croton velutinus, in MCF‑7 Cells}},
  author = {Renata A. de Abrantes and Sâmia S. Duarte and Rafael C. Ferreira and Ana Paula G. M. Farias and Geraldo M. W. Amorim and Paulo B. A. Loureiro and Ramon R. M. de Souza and Valgrícia M. de Sousa and Gabriela B. de Lyra and Isabela C. F. Silva and Lucas S. Abreu and Eudes da S. Velozo and Juan C. R. Gonçalves and Marcelo S. da Silva and Josean F. Tavares and Marianna V. Sobral},
  journal = {ACS omega},
  year = {2026},
  month = oct,
  doi = {10.1021/acsomega.6c04220},
  url = {https://europepmc.org/article/PMC/PMC13670846},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Signaling Pathways Mediating the Cytotoxicity of (E)-4-(1-Epoxy-7,8-propenyl)phenyl Benzoate, a Phenylpropanoid from Croton velutinus, in MCF‑7 Cells
AU  - Renata A. de Abrantes
AU  - Sâmia S. Duarte
AU  - Rafael C. Ferreira
AU  - Ana Paula G. M. Farias
AU  - Geraldo M. W. Amorim
AU  - Paulo B. A. Loureiro
AU  - Ramon R. M. de Souza
AU  - Valgrícia M. de Sousa
AU  - Gabriela B. de Lyra
AU  - Isabela C. F. Silva
AU  - Lucas S. Abreu
AU  - Eudes da S. Velozo
AU  - Juan C. R. Gonçalves
AU  - Marcelo S. da Silva
AU  - Josean F. Tavares
AU  - Marianna V. Sobral
PY  - 2026
DA  - 2026/10/02
JO  - ACS omega
DO  - 10.1021/acsomega.6c04220
UR  - https://europepmc.org/article/PMC/PMC13670846
AB  - Natural products represent an important source of candidates for breast cancer therapy. Here, we investigated the antitumor activity of (E)-4-(1-epoxy-7,8-propen)phenylbenzoate (CV2), a phenylpropanoid isolated from Croton velutinus roots, in MCF-7 breast cancer cells and evaluated its toxicity profile in nontumor cells and zebrafish embryos. CV2 exhibited potent cytotoxic activity against MCF-7 cells (IC50= 4.63 ± 0.16 μM) and showed selectivity relative to nontumorigenic MCF-10A cells (SI = 9.69). CV2 also induced apoptosis, increased intracellular ROS levels, and modulated MAPK, NF-κB, and PKB/AKT signaling pathways. Pretreatment with N-acetylcysteine or MAPK inhibitors significantly attenuated CV2-induced cytotoxicity, supporting the involvement of oxidative stress and MAPK signaling in its biological effects. In toxicity studies, CV2 exhibited cytotoxicity toward peripheral blood mononuclear cells (PBMCs; IC50 = 1.75 ± 0.06 μM) and an LC50 of 3.07 μM in zebrafish embryos, accompanied by alterations in oxidative stress-related enzymes. Collectively, these findings demonstrate that CV2 possesses significant antitumor activity against breast cancer cells while highlighting the need for further studies to better define its safety profile and therapeutic potential.
SN  - 2470-1343
ER  -