RESUMEN
UNLABELLED: The cytotoxic compound Altersolanol A, an anthraquinone derivative was isolated from PM0409092 a fungus of Nyctanthes arbor-tristis (family Oleaceae). It was identified as a Phomopsis sp. by DNA amplification and sequencing of the ITS region. The chemical structure of Altersolanol A was elucidated from its physicochemical properties, 2D NMR spectroscopy and other spectroscopic data. The compound has in vitro cytotoxic activity against 34 human cancer cell lines with mean IC50 (IC70) values of 0.005 µg ml(-1) (0.024 µg ml(-1)) respectively. Altersolanol A, a kinase inhibitor, induces cell death by apoptosis through the cleavage by Caspase-3 and -9 and by decreased anti-apoptotic protein expression. There are several previous reports of the anticancer activity of Altersolanol A, but we report here an extensive study using 36 cell lines which gives wider spectrum of results. SIGNIFICANCE AND IMPACT OF THE STUDY: This study confirms the cytotoxic potential of Altersolanol A isolated from the endophyte Phomopsis sp. (PM0409092) of the plant Nyctanthes arbor-tristis. The compound exhibits in vitro cytotoxicity against 34 human cancer cell lines with mean IC50 (IC70) value of 0.005 µg ml(-1) (0.024 µg ml(-1)). This is an in-depth report of Altersolanol A against a panel of 34 human cancer cell lines and extends observations from previous studies indicating that Altersolanol A can be used for the development of chemotherapeutics. Altersolanol A, a kinase inhibitor, induces cell death by apoptosis through the cleavage of Caspase-3 and -9 and by decreased anti-apoptotic protein expression.
Asunto(s)
Antraquinonas/farmacología , Antineoplásicos/farmacología , Ascomicetos/metabolismo , Neoplasias/tratamiento farmacológico , Oleaceae/microbiología , Antraquinonas/metabolismo , Antineoplásicos/metabolismo , Apoptosis/efectos de los fármacos , Ascomicetos/aislamiento & purificación , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Línea Celular Tumoral , Endófitos/metabolismo , HumanosAsunto(s)
Antineoplásicos/uso terapéutico , Artefactos , Tecnología Biomédica , Proliferación Celular/efectos de los fármacos , Muérdago , Neoplasias/tratamiento farmacológico , Fitoterapia , Terapias Complementarias , Humanos , Extractos Vegetales/uso terapéutico , Células Tumorales Cultivadas/efectos de los fármacosRESUMEN
The in vitro antiproliferative or stimulatory activity of an aqueous mistletoe extract (AME) with a defined content of bioactive mistletoe lectin (ML) was investigated in 6 human tumor cell lines, including two melanomas and leiomyosarcomas, each of which had previously been reported to show evidence of growth stimulation if treated with low concentrations of isolated ML. The effects of AME were compared to that of the standard cytotoxic agent adriamycin (ADR) using the well established propidium iodide and sulforhodamin B proliferation assays. The AME concentrations used ranged from 0.5 pg to 5 ng (0.82 fMol-85 pM) bioactive ML/ml in melanoma (HT-144, SK-MEL-28) and leiomyosarcoma (SK-MLS-1, S-UT-1B) cell lines and from 0.1-100 ng ML/ml (1.7 pM-1.7 nM) in MCF-7 breast cancer and SW620 colon carcinoma cell lines, respectively. The influence of AME on cell growth was determined at various time-points from 24 hours to 6 days of exposure. We found a time- and cell line-dependent inhibition of tumor cell growth, but no reproducible stimulation of tumor cell proliferation. Inhibitory concentrations 50% (IC50) for e.g. the SK-MEL-28 melanoma cell line, decreased from 4.1 ng ML/ml at 24 hours to 0.16 ng ML/ml at 72 hours and 0.18 ng ML/ml at 5 days. Our data clearly demonstrate that, by applying scientifically valid methods and procedures, the standardized AME did not stimulate tumor cell proliferation but showed time- and concentration-dependent antiproliferative effects.