Pleurotus highking Mushroom Induces Apoptosis by Altering the Balance of Proapoptotic and Antiapoptotic Genes in Breast Cancer Cells and Inhibits Tumor Sphere Formation

Abstract

Background and objectives: Mushrooms that have medicinal properties are part of many traditional diets. The aim of the present study was to use the human breast cancer cell line MCF-7 to investigate the anticancer activity of Pleurotus highking mushroom purified extract fraction-III (PEF-III) and to elucidate the possible mechanism of that activity. Materials and Methods: The effects of PEF-III on cell proliferation and viability were evaluated by a colony formation assay and an MTT assay, respectively. Cell morphological changes, annexin-V phycoerythrin and propidium iodide (PI) staining, DNA fragmentation, and caspase 3/7 activity assays were performed to determine the induction of apoptosis by PEF-III. The genes responsible for regulation of apoptosis were analyzed by means of Western blot analysis. In vitro tumor sphere formation assay was performed using a 3D sphere culture system. Results: PEF-III significantly reduced the proliferation and viability of MCF-7 cells. Cell shrinkage and rounding, and annexin-V phycoerythrin and PI staining followed by flow cytometry indicated that the cell death was due to apoptosis. Additionally, a laddering DNA pattern and increased levels of caspase-3/7 enzyme also corroborated the notion of apoptosis-mediated cell death. This incidence was further confirmed by upregulation of proapoptotic genes (p53 and its target gene, Bax) and downregulation of the expression of an antiapoptotic gene (Bcl-2). PEF-III also reduced the size and number of the tumor spheres in 3D culture conditions. Conclusions: The anticancer activity of PEF-III is due to induction of apoptosis by a shift in the balance of proapoptotic and antiapoptotic genes. Therefore, the findings of the present study may open a path to exploring potential drug candidates from the P. highking mushroom for combating breast cancer.

Wild Medicinal Fungi: Phallus Impudicus-induced Telomere Damage Triggers p21/p53 and p16-dependent Cell Cycle Arrest and Drives to Male Fertility Reduction in Vitro

“…Here, we observed a clear relationship between caspase-3/Bcl-2, more speci cally a signi cant upregulation of cleaved caspase-3 with a simultaneous decrease in Bcl-2 synthesis. Similar observations were done by other researchers (Lee et al 2009;Haque and Islam 2019). In addition, apoptosis induction was related to increased pro-apoptotic Bax protein expression, inhibition of Bcl-2, and activation of key mediators of signaling in fungi -p38 MAPKs (Chen et al 2010).…”

Stevia Eupatoria and Stevia Pilosa Extracts Inhibit the Proliferation and Migration of Prostate Cancer Cells

“…Few treatments are approved, like enzalutamide, that delay the progression of the illness while maintaining a good quality of life [8]. However, the resistance to therapy and risk of recurrence has led to the search for new effective anticancer compounds, including those from medicinal plants [9]. Stevia is a perennial herbaceous shrub that grows from the Southwest USA to Northern Argentina and is traditionally used as a medicinal plant [10].…”

Bioactive Abietane-Type Diterpenoid Glycosides from Leaves of Clerodendrum infortunatum (Lamiaceae)

“…The breast cancer cell proliferation activity of the tested compounds was assessed using a colony formation assay [ 41 ]. Approximately 400 viable Hs578T and MDA-MB-231 cells were seeded in a 10 cm culture plate containing DMEM medium without or with the tested compounds (at their respective IC 50 concentration), and incubated for 2 weeks.…”