Isolation and identification of three new chromones from the leaves of Pimenta dioica with cytotoxic,oestrogenic and anti-oestrogenic effects |
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| Authors: | Brian J. Doyle Temitope O. Lawal Tracie D. Locklear Lorraina Hernandez Alice L. Perez Udeshi Patel |
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| Affiliation: | 1. Department of Biology and Department of Biochemistry, Alma College, Alma, MI, USA;2. Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, IL, USA;3. Department of Pharmaceutical Microbiology, University of Ibadan, Ibadan, Nigeria;4. Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA;5. Centro de Investigaciones en Productos Naturales (CIPRONA), Natural Products Research Center, University of Costa Rica, San Jose, Costa Rica;6. Department of Pharmacy Practice, PAHO/WHO Collaborating Centre for Traditional Medicine, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA |
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| Abstract: | Context: Pimenta dioica (L.) Merr. (Myrtaceae) is used in Costa Rican traditional medicine for women’s health. Our previous work showed that P. dioica extracts were oestrogenic.Objectives: This work identifies phytochemicals from P. dioica that are responsible for the plant’s oestrogen-like activities.Materials and methods: P. dioica leaves were collected in Costa Rica in 2005. Fractions resulting from chromatographic separation of a methanol extract were tested at 50?μg/mL in a competitive oestrogen receptor-binding assay. Active compounds were isolated by HPLC and identified by NMR and MS. Pure compounds were tested at 1?μM in the oestrogen-responsive SEAP reporter gene assay. The effects on cell viability, cytotoxicity and apoptosis were investigated in breast cancer (MCF-7 and SK-BR3) and gastric cancer (AGS and NCI-N87) cell lines using the ApoTox-Glo and Caspase-Glo assays and qPCR.Results: Quercitrin and three new chromones, including a 2-phenoxychromone, 6,8-di-C-methylcapillarisin (1) were isolated and identified. Compound 1 caused a 6.2-fold increase in SEAP expression at 1?μM (p?2 caused a 6.0-fold increase in SEAP, inhibited the growth of MCF-7, AGS and NCI-N87 cells (IC50 54.27, 38.13 and 51.22?μg/mL, respectively), and induced apoptosis via caspase 8 and increased the Bax/Bcl-2 mRNA ratio in MCF-7 cells. Compound 3 was anti-oestrogenic in MCF-7 cells.Discussion and conclusions: Compounds from P. dioica have oestrogenic, anti-oestrogenic and cytotoxic effects that may explain the ethnomedical use of this plant. |
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| Keywords: | Allspice apoptosis breast cancer caspase Costa Rica ethnomedicine oestrogen Latin America menopause |
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