Affiliations 

  • 1 Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, USM, 11800 Pulau Pinang, Malaysia
  • 2 Dental Research & Training Unit, and Oral Cancer Research and Coordinating Centre (OCRCC), Faculty of Dentistry, University of Malaya, 50603 Kuala Lumpur, Malaysia
  • 3 Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research (LIMBR), School of Medicine (SoM), Faculty of Health, Institute for Frontier Materials (IFM), Deakin University, Waurn Ponds, VIC 3217 Australia
  • 4 Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, USM, 11800 Pulau Pinang, Malaysia. Electronic address: srisasidharan@yahoo.com
J Ethnopharmacol, 2017 Apr 06;201:42-55.
PMID: 28263848 DOI: 10.1016/j.jep.2017.02.041

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 24h. 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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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