Phaleria macrocarpa (Boerl.) fruit induce G0/G1 and G2/M cell cycle arrest and apoptosis through mitochondria-mediated pathway in MDA-MB-231 human breast cancer cell. (6th April 2017)

• Record Type: Journal Article
• Authors: Kavitha, Nowroji; Ein Oon, Chern; Chen, Yeng; Kanwar, Jagat R.; Sasidharan, Sreenivasan
• Is Part Of: Journal of ethnopharmacology. Volume 201(2017)
• Page Start: 42
• Page End: 55
• Publication Date: 2017-04-06
• Subjects: Cells cycle arrest -- Apoptosis -- Caspase, p53, cytochrome c; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2017.02.041
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Phaleria macrocarpa (Scheff) Boerl, is a well-known folk medicinal plant in Indonesia. Traditionally, P. macrocarpa has been used to control cancer, impotency, hemorrhoids, diabetes mellitus, allergies, liver and hearth disease, kidney disorders, blood diseases, acne, stroke, migraine, and various skin diseases. Aim of the study: The purpose of this study was to determine the in situ cytotoxicity effect P. macrocarpa fruit ethyl acetate fraction (PMEAF) and the underlying molecular mechanism of cell death. Materials and methods: MDA-MB-231 cells were incubated with PMEAF for 24 h. Cell cycle and viability were examined using flow cytometry analysis. Apoptosis was determined using the Annexin V assay and also by fluorescence microscopy. Apoptosis protein profiling was detected by RayBio® Human Apoptosis Array. Results: The AO/PI staining and flow cytometric analysis of MDA-MB-231 cells treated with PMEAF were showed apoptotic cell death. The cell cycle analysis by flow cytometry analysis revealed that the accumulation of PMEAF treated MDA-MB-231 cells in G0 /G1 and G2 /M-phase of the cell cycle. Moreover, the PMEAF exert cytotoxicity by increased the ROS production in MDA-MB-231 cells consistently stimulated the loss of mitochondrial membrane potential (∆Ψm ) and induced apoptosis cell death by activation of numerous signalling proteins. The results from apoptosis protein profiling array evidenced that PMEAF stimulated the expression of 9 pro-apoptotic proteins (Bax, Bid, caspase 3, caspase 8, cytochrome c, p21, p27, p53 and SMAC) and suppressed the 4 anti-apoptotic proteins (Bcl-2, Bcl-w, XIAP and survivin) in MDA-MB-231 cells. Conclusion: The results indicated that PMEAF treatment induced apoptosis in MDA-MB-231 cells through intrinsic mitochondrial related pathway with the participation of pro and anti-apoptotic proteins, caspases, G0 /G1 and G2 /M-phases cell cycle arrest by p53-mediated mechanism. Graphical abstract: Highlights: The mode of PMEAF-induced cell death and the mechanisms involved were examined. PMEAF induced mainly apoptotic death of breast cancer MDA-MB-231 cells. PMEAF induced mitochondrial-mediated and caspase-dependent apoptosis. p53-mediated pathways are involved in PMEAF-mediated apoptosis in the MDA-MB-231 cells.