(6E,10E) Isopolycerasoidol and (6E,10E) Isopolycerasoidol Methyl Ester, Prenylated Benzopyran Derivatives from Pseuduvaria monticola Induce Mitochondrial-Mediated Apoptosis in Human Breast Adenocarcinoma Cells

• Published in: PloS one Vol. 10; no. 5; p. e0126126
• Main Authors: Taha, Hairin, Looi, Chung Yeng, Arya, Aditya, Wong, Won Fen, Yap, Lee Fah, Hasanpourghadi, Mohadeseh, Mohd, Mustafa A, Paterson, Ian C, Mohd Ali, Hapipah
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 06.05.2015; Public Library of Science (PLoS)
• Subjects: Adenocarcinoma; Adenocarcinoma - drug therapy; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Alternative medicine; Annonaceae - chemistry; Anticancer properties; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - isolation & purification; Antineoplastic Agents, Phytogenic - pharmacology; Antitumor agents; Apoptosis; Apoptosis - drug effects; Benzopyrans - chemistry; Benzopyrans - isolation & purification; Benzopyrans - pharmacology; Biology; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer; Cancer cells; Cancer research; Caspase; Caspase-3; Caspases - metabolism; Cell death; Cell Line, Tumor; Cell Membrane Permeability - drug effects; Chemistry; Cytometry; Cytotoxicity; Dentistry; Down-Regulation - drug effects; Epithelial cells; Female; Flow cytometry; Gene expression; Genes, bcl-2 - drug effects; Health aspects; Humans; Leaves; Magnetic Resonance Spectroscopy; MAP kinase; MCF-7 Cells; Medical research; Membrane permeability; Membrane potential; Membrane Potential, Mitochondrial - drug effects; Mitochondria; NMR; Nuclear magnetic resonance; Nuclei; Oral cancer; Oxidative stress; p38 Mitogen-Activated Protein Kinases - metabolism; Permeability; Pharmacology; Physiological aspects; Phytochemicals; Prostate cancer; Pseuduvaria monticola; Reactive Oxygen Species - metabolism; Science; Studies
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0126126

Phytochemicals from Pseuduvaria species have been reported to display a wide range of biological activities. In the present study, a known benzopyran derivative, (6E,10E) isopolycerasoidol (1), and a new benzopyran derivative, (6E,10E) isopolycerasoidol methyl ester (2), were isolated from a methanol extract of Pseuduvaria monticola leaves. The structures of the isolated compounds were elucidated by spectroscopic methods including 1D and 2D NMR, IR, UV, and LCMS-QTOF, and by comparison with previously published data. The anti-proliferative and cytotoxic effects of these compounds on human breast cancer cell-lines (MCF-7 and MDA-MB-231) and a human normal breast epithelial cell line (MCF-10A) were investigated. MTT results revealed both (1) and (2) were efficient in reducing cell viability of breast cancer cells. Flow cytometry analysis demonstrated that (1) and (2) induced cell death via apoptosis, as demonstrated by an increase in phosphotidylserine exposure. Both compounds elevated ROS production, leading to reduced mitochondrial membrane potential and increased plasma membrane permeability in breast cancer cells. These effects occurred concomitantly with a dose-dependent activation of caspase 3/7 and 9, a down-regulation of the anti-apoptotic gene BCL2 and the accumulation of p38 MAPK in the nucleus. Taken together, our data demonstrate that (1) and (2) induce intrinsic mitochondrial-mediated apoptosis in human breast cancer cells, which provides the first pharmacological evidence for their future development as anticancer agents.