<strong>Selective Cytotoxic Effects of <em>Annona Squamosa Leaves </em>against Breast Cancer Cells via Apoptotic Signaling Proteins</strong>

Abstract

: Annona squamosa L. is an important medicinal plant used in traditional medicine for the treatment of various diseases. Different parts of A. squamosa L. have various therapeutic effects; however, the anticancer activity of the leaves has not yet been identified. In vitro, MTT, nuclear staining, and LDH assays were used to evaluate cell survival and proliferation in cells exposed to the extracts. The effect of the extracts on cell migration was investigated using a monolayer wound repair assay, and the apoptotic effects were evaluated using flow cytometry. A breast cancer model was used to study the effect of the extract on the tumor size, and the expression of different proliferative and apoptotic markers was evaluated by immunohistochemical analysis. At a concentration of 100 &amp;micro;g/mL, A. squamosa leaf extracts exerted strong antiproliferative and cytotoxic effects against various cell lines. The extracts reduced wound closure and strongly induced apoptosis. In vivo study, rats were sacrificed 24 h after the last injection, and tumor size, as well as the expression of proliferative and apoptotic markers, were observed to be greatly affected by treatment with the extracts. Therefore, A. squamosa leaf extract may be developed as a potential novel drug to treat breast cancer in the future

Custard Apple (Annona squamosa L.) Leaves: Nutritional Composition, Phytochemical Profile, and Health-Promoting Biological Activities

“…Leaves of Annona squamosa have a number of chemical compounds belonging to diverse groups, including phenolics, annonaceous acetogenins, saponins, flavonoids, alkaloids, glycosides, alkaloids, steroids, and terpenoids [ 62 ]. A study was conducted to investigate the in vivo and in vitro anti-breast cancer activity of ASL extracts [ 40 ]. Leaf extract at a concentration of 100 µg/mL exhibited strong cytotoxic and antiproliferative activities against breast cancer cell lines (MCF-7 and MDA-MB-231).…”

Biochemical and molecular mechanisms of Annona sp. fruits extract in Ehrlich ascites carcinoma-bearing mice

“…It has been reported that the A. squamosa leaf extract increased the expression of proliferative and apoptotic markers, which in turn enhanced the extract's anticancer effect on breast cancer cell lines. Additionally, they conducted an in vivo investigation, and it was found that the treatment of rats with the extracts had an impact on the tumor size, proliferative, and apoptotic indicators [16]. Furthermore, a previous study could be suggested that Graviola exerts its antitumor effect throughout the regulation of the tumor cell cycle as well as inducing apoptotic signals including an increase in antiapoptotic Bcl-2 gene expression [46].…”

“…both in vitro and in vivo [14]. Additionally, it was found that the treatment of rats with this fruit extract had an impact on the tumor size, proliferative, and apoptotic indicators [16]. The Annona muricata extract has selective inhibitory activity against cancer cells that was modulated by acerogenin activity in the complex I mitochondrial electron transport chain, hampering the process of ATP formation needed for cancer cell growth [17].…”

Prediction of Biological Activities of A. Squamosa Bioactive Compounds by-Silico Design

“…It can be seen from the structure-activity relationship (SAR) that A. squamosa and its biologically active compound have cytotoxic activity against several different cancer-causing cell lines [21]. In 2021, Acetogenins, Isoquinoline, Quercetin-3-O-glucoside, phenanthrene and annoreticuin were isolated from the three-fold antioxidant activity of A. squamosa having activity on breast cancer [22]. Considering all these promising results, several compounds have been isolated from commercially available quercetin 3 O glucoside.…”