title: Polyalthia longifolia Methanolic Leaf Extracts (PLME) induce apoptosis, cell cycle arrest and mitochondrial potential depolarization by possibly modulating the redox status in hela cells.
abstract: Medicinal plants have been accepted as a gold mine, with respect to the diversity of their phytochemicals. Many medicinal plants extracts are potential anticancer agents. Polyalthia longifolia var. angustifolia Thw. (Annonaceae) is one of the most significant native medicinal plants and is found throughout Malaysia. Hence, the present study was intended to assess the anticancer properties of P. longifolia leaf methanolic extract (PLME) and its underlying mechanisms. The Annexin V/PI flow cytometry analysis showed that PLME induces apoptosis in HeLa cells in dose-dependent manner whereas the PI flow cytometric analysis for cell cycle demonstrated the accumulation of cells at sub G0/G1, G0/G1 and G2/M phases. Investigation with JC-1 flow cytometry analysis indicated increase in mitochondria membrane potential depolarisation corresponding to increase in PLME concentrations. PLME was also shown to influence intracellular reactive oxygen species (ROS) by exerting anti-oxidant (half IC50) and pro-oxidant (IC50and double IC50) affect against HeLa cells. PLME treatment also displayed DNA damage in HeLa cells in concentration depended fashion. The proteomic profiling array exposed the expression of pro-apoptotic and anti-apoptotic proteins upon PLME treatment at IC50concentration in HeLa cells. Pro-apoptotic proteins; BAX, BAD, cytochrome c, caspase-3, p21, p27 and p53 were found to be significantly up-regulated while anti-apoptotic proteins; BCL-2 and BCL-w were found to be significantly down-regulated. This investigation postulated the role of p53 into mediating apoptosis, cell cycle arrest and mitochondrial potential depolarisation by modulating the redox status of HeLa cells.
authors.affiliation: Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, USM 11800, Pulau Pinang, Malaysia.
authors.forename: Soundararajan
authors.initials: S
authors.lastname: Vijayarathna
authors.affiliation: Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, USM 11800, Pulau Pinang, Malaysia.
authors.forename: Chern Ein
authors.initials: CE
authors.lastname: Oon
authors.affiliation: Dental Research & Training Unit, and Oral Cancer Research and Coordinating Centre (OCRCC), Faculty of Dentistry, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Yeng
authors.initials: Y
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Jagat R
authors.initials: JR
authors.lastname: Kanwar
authors.affiliation: Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, USM 11800, Pulau Pinang, Malaysia. Electronic address: srisasidharan@yahoo.com.
authors.forename: Sreenivasan
authors.initials: S
authors.lastname: Sasidharan
mesh_terms: D029061:Annonaceae / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry*; D017382:Reactive Oxygen Species
chemical_list: D010936:Plant Extracts; D017382:Reactive Oxygen Species
keywords: Apoptosis; Apoptotic protein; Cell-cycle arrest; Cytotoxicity; DNA fragmentation; P. longifolia