Apoptosis Induced by (+)-Betulin Through NF-κB Inhibition in MDA-MB-231 Breast Cancer Cells.

Abstract

BACKGROUND/AIM:

This study aimed to uncover the effects of (+)-betulin on the NF-κB-apoptotic pathway in MDA-MB-231 cells, and determine its toxicity and protein expression in vivo.

MATERIALS AND METHODS:

Cell cytotoxicity and toxicity were determined using the SRB assay and a zebrafish model, respectively. Western blot, mitochondrial transmembrane potential (MTP), and computational modeling analysis were performed.

RESULTS:

(+)-betulin inhibited the growth of MDA-MB-231 cells, but did not induce toxicity in zebrafish. (+)-Betulin inhibited the activity of NF-κB p65 in silico and in vitro. In cells, (+)-betulin down-regulated NF-κB p50 and 65, IKKα and β, ICAM-1 and bcl-2 expressions. Cell co-treatment with (+)-betulin and TNFα increased the (+)-betulin cytotoxic potential. Moreover, (+)-betulin induced the loss of MTP. Furthermore, (+)-betulin, in zebrafish, down-regulated the expression of NF-κB p65, IKKα, ΙΚΚβ and procaspase-3.

CONCLUSION:

The results contribute to the understanding of the mode of action on apoptosis induction by inhibiting NF-κB pathway in MDA-MB-231 cells.

• Authors: Gerardo D Anaya-Eugenio, Nicole A Eggers, Yulin Ren, JosÉ Rivera-ChÁvez, A Douglas Kinghorn, Esperanza J Carcache DE Blanco
• Journal: Anticancer research (Anticancer Res) Vol. 40 Issue 12 Pg. 6637-6647 (Dec 2020) ISSN: 1791-7530 [Electronic] Greece
• PMID: 33288558 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• NF-kappa B
• Proto-Oncogene Proteins c-bcl-2
• Triterpenes
• Tumor Necrosis Factor-alpha
• betulin

Topics

• Animals
• Apoptosis (drug effects)
• Breast Neoplasms (pathology)
• Cell Line, Tumor
• Female
• Humans
• Membrane Potential, Mitochondrial (drug effects)
• Molecular Docking Simulation
• NF-kappa B (antagonists & inhibitors, metabolism)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Signal Transduction (drug effects)
• Triterpenes (chemistry, pharmacology)
• Tumor Necrosis Factor-alpha (pharmacology)
• Zebrafish