@Article{biocell.2023.029076,
AUTHOR = {MARIA-LUISA VEISAGA, MARIAM AHUMADA, STACY SORIANO, LEONARDO ACUNA, WEI ZHANG, IVY LEUNG, ROBERT BARNUM, MANUEL A. BARBIERI},
TITLE = {Anti-proliferative effect of <i>Annona</i> extracts on breast cancer cells},
JOURNAL = {BIOCELL},
VOLUME = {47},
YEAR = {2023},
NUMBER = {8},
PAGES = {1835--1852},
URL = {http://www.techscience.com/biocell/v47n8/53794},
ISSN = {1667-5746},
ABSTRACT = {<b>Backgorund: </b>Fruits and seed extracts of <i>Annona montana</i> have significant cytotoxic potential in several cancer
cells. This study evaluates the effect of <i>A. montana</i> leaves hexane extract on several signaling cascades and gene expression
in metastatic breast cancer cells upon insulin-like growth factor-1 (IGF-1) stimulation. <b>Methods:</b> 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 <i>A. montana</i> leaves hexane extract. <b>Results: </b><i>A. montana</i> 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. <b>Conclusion:</b> Our study indicates that <i>A. montana</i> 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.},
DOI = {10.32604/biocell.2023.029076}
}