Open Access

ARTICLE

Anti-proliferative effect of Annona extracts on breast cancer cells

MARIA-LUISA VEISAGA^1,2, MARIAM AHUMADA², STACY SORIANO², LEONARDO ACUNA³, WEI ZHANG³, IVY LEUNG², ROBERT BARNUM², MANUEL A. BARBIERI^1,2,3,4,5,*

1 Biomolecular Sciences Institute, Florida International University, Miami, 33199, USA
2 Department of Biological Sciences, Florida International University, Miami, 33199, USA
3 Biochemistry Ph.D. Program, Florida International University, Miami, 33199, USA
4 Fairchild Tropical Botanic Garden, Coral Gables, 33156, USA
5 International Center of Tropical Botany, Florida International University, Miami, 33199, USA

* Corresponding Author: Manuel A. Barbieri,

(This article belongs to the Special Issue: Natural Products for Chronic Inflammatory Diseases: Pharmacology and Toxicology)

BIOCELL 2023, 47(8), 1835-1852. https://doi.org/10.32604/biocell.2023.029076

Received 31 January 2023; Accepted 01 June 2023; Issue published 28 August 2023

Abstract

Backgorund: Fruits and seed extracts of Annona montana have significant cytotoxic potential in several cancer cells. This study evaluates the effect of A. montana leaves hexane extract on several signaling cascades and gene expression in metastatic breast cancer cells upon insulin-like growth factor-1 (IGF-1) stimulation. Methods: MTT assay was performed to determine the proliferation of cancer cells. Propidium iodide staining and flow cytometry analysis of Annexin V binding was utilized to measure the progression of the cell cycle and the induction of apoptosis. Protein expression and phosphorylation were determined by western blotting analysis to examine the underlying cellular mechanism triggered upon treatment with A. montana leaves hexane extract. Results: A. montana leaves hexane (subfraction V) blocked the constitutive stimulation of the PI3K/mTOR signaling pathways. This inhibitory effect was associated with apoptosis induction as evidenced by the positivity with Annexin V and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNNEL) staining, activation of caspase-3, and cleavage of PPAR. It also limited the expression of various downstream genes that regulate proliferation, survival, metastasis, and angiogenesis (i.e., cyclin D1, survivin, COX-2, and VEGF). It increased the expression of p53 and p21. Interestingly, we also observed that this extract blocked the activation of AKT and ERK without affecting the phosphorylation of the IGF-1 receptor and activation of Ras upon IGF-1 stimulation. Conclusion: Our study indicates that A. montana leaves (sub-fraction V) extract exhibits a selective anti-proliferative and proapoptotic effect on the metastatic MDA-MB-231 breast cancer cells through the involvement of PI3K/AKT/mTOR/S6K1 pathways.

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