<p>Effects of <em>Annona muricata</em> Extract on Triple-Negative Breast Cancer Cells Mediated Through EGFR Signaling</p>

Abstract

Purpose: To evaluate the antiproliferative activity and the mechanisms of action of Annona muricata ethyl acetate (AMEA) extract and one of its active fractions on BT-20 TNBC cells. Methods: The triple-negative human breast cancer BT-20 cells were used. After the preparation and extraction of Annona muricata ethyl acetate (AMEA), the ethyl acetate extract was exposed to a preparative thin layer chromatography (TLC) plate. From this preparative TLC plate, eight individual bands were collected. Each band was scraped and removed from the plate and soaked in ethyl acetate. After filtration, all eight fractions were then tested on the BT-20 TNBC cells using the MTS cell viability assay. The expressions of EGFR, p-EGFR, AKT, p-AKT, MAPK, p-MAPK, cyclin D1, and NF-κB p65 were measured using Western blot analysis. Results: The AMEA showed a significant decrease in NF-κB p65 protein expression and BT-20 cell viability, as determined via the MTS assay. Furthermore, the AMEA was subjected to preparative thin layer chromatography (TLC), and eight fractions were obtained. From the eight fractions, only fraction 4 (F4) showed a significant reduction in cell viability in the MTS assay. Immunoblotting analysis revealed that AMEA and F4 formed an antiproliferative effect. These effects were complemented by a downregulation of cyclin D1 assembly, causing cell-cycle arrest at the G1/S phase. Furthermore, NF-κB was measured because of its involvement in the progression of cancers. Conclusion: The antiproliferative influence is produced through EGFR-mediated signaling pathways, which include AKT, MAPK, NF-κB, and cyclin D1 inhibition. Further studies will be required to demonstrate the possible applications of this natural product in breast cancer therapy.

Antitumor Potential of Annona muricata Linn. An Edible and Medicinal Plant in Mexico: In Vitro, In Vivo, and Toxicological Studies

“…Acetogenins have been identified as one of the major bioactive compounds of A. muricata with activity on several cancer cell lines [15,16]. The ethanol extracts obtained from aerial parts from A. muricata in combination with doxorubicin showed important cytotoxic activity on 4T1 cells and other cancer cell lines [15][16][17][18][19][20][21][22]. Although there is an extensive amount of information about the cytotoxic properties of A. muricata, no information is available regarding its anti-cancer potential in specifically breast cancer using the extracts of plants collected in different periods of the year, and regarding the location of the place of recollection and its influences on their pharmacological and toxic properties.…”

Drug Delivery of Natural Products Through Nanocarriers for Effective Breast Cancer Therapy: A Comprehensive Review of Literature

“… 151–154 These anti-BC activities have been linked to the regulation of immune system, the reduction of inflammation, the suppression of various signalling pathways (eg, epidermal growth factor receptor [EGFR], mitogen-activated protein kinase [MAPK], phosphoinositide 3-kinase/protein kinase B [PI3K/AKT] and nuclear factor-kappa B [NF-κB]), the modulation of cell cycle regulators, as well as the stimulation of ROS generation and consequent induction of caspase-dependent apoptosis. 151 , 153 , 154 …”

The Natural Products and Extracts: Anti‐Triple‐Negative Breast Cancer in Vitro

“…Fraction 4 (F4) showed a significant reduction in cell viability in the MTS assay. AMEA and F4 formed an antiproliferative effect by a downregulation of cyclin D1 assembly, causing cell‐cycle arrest at the G1/S phase [87] …”