Cytotoxic Guanidine Alkaloids from Pterogyne nitens (original) (raw)
Carcinogenic effects of ptaquiloside in bracken fern and related compounds
British Journal of Cancer, 2000
Consumption of the bracken fern Pteridium aquilinum by cattle has been shown to induce bladder and intestinal carcinomas in cattle and to cause a number of diseases in other farm animals. An unstable glucoside named ptaquiloside, containing a reactive cyclopropane ring, has been isolated from the fern and its potent carcinogenicity proven. Nineteen of 31 ferns tested by chemotaxonomic methods in Japan have been found to contain potentially carcinogenic ptaquilosides as have Cheilanthes sieberi and Pteridium esculentum. Hydrolysis of ptaquilosides leads to pterosins; under milder conditions a dienone which is believed to be the primary carcinogen is obtained. Hypacrone, a sesquiterpine containing a reactive cyclopropane ring, has been isolated from Hypolepis punctata and its structure proved by synthesis. Illudins, structurally similar to ptaquiloside, have been isolated from the basidiomycete Omphalotus illudens. These give anti-tumour activity and similar reactivity with nucleophiles to ptaquiloside. Compound CC-1065, a highly toxic antibiotic also containing a cyclopropane ring, has been isolated from Streptomyces zelensis. The mechanism of its reactivity with DNA has been compared to that of ptaquiloside and the small structural differences between carcinogenic and anti-tumour activity discussed. Both CC-1065 and adozelesin, a synthetic analogue with anti-tumour activity, have been shown to alkylate the N-3 atom of adenine in a certain sequence of DNA. The reactivity of cysteine with ptaquilosides and illudins is discussed, as is the role of cysteine alkylating agents in apoptosis.
Purification of ptaquiloside, a carcinogen from Pteridium aquilinum
Phytochemistry, 1995
Ptaquiloside, the major carcinogen of bracken fern (Pteridium aquilinum), was isolated in high yield from milled freeze-dried plant material. Because the compound is unstable, a new method was devised to avoid steps which caused loss of activity. Modern multipulse and 2D NMR techniques allowed confirmation of the previously proposed structure, although some assignments were shown to be incorrect.
Antigenotoxic, Antioxidant and Lymphocyte Induction Effects Produced by Pteropodine
Basic & Clinical Pharmacology & Toxicology, 2009
Pteropodine is a heterohimbine-type oxindole alkaloid specifically isolated from 'Cat's claw' (Uncaria tomentosa), a plant that has shown cytostatic, anti-inflammatory and antimutagenic properties and is used in traditional medicine to cure a number of diseases. In this report, we studied the ability of pteropodine to decrease the rate of sister-chromatid exchanges and micronucleated polychromatic erythrocytes in mice administered doxorubicin. We also determined its capacity to induce lymphocyte production in mice as well as its free radical scavenging potential by applying the DPPH assay. We found pteropodine (100-600 mg/kg) to significantly decrease the frequency of sister-chromatid exchanges and micronucleated polychromatic erythrocytes in mice administered with 10 mg/kg of doxorubicin. Furthermore, we determined that pteropodine partially corrected bone marrow cytotoxicity induced by doxorubicin, as it showed an improvement in the rate of polychromatic erythrocytes. Besides, 600 mg/kg of pteropodine increased 25.8% of the production of lymphocytes over the control value along a 96-hr assay, and it exhibited a strong capacity to trap the DPPH-free radical (98.26% with 250 μ g/ml). Our results establish that pteropodine is an effective antimutagen in the model used, and suggest that pteropodine deserves further research in the area of cell protective potential and its mechanism of action.
Ptaquiloside‑induced cytotoxicity in Crandall feline kidney and HGC‑27 cells
Oncology Letters, 2014
Ptaquiloside (PTA) is a potent genotoxic carcinogenic compound, which is found in bracken ferns and predominantly causes gastric tumors in humans, as well as bladder tumors and chronic enzootic hematuria in cattle. The underlying molecular mechanisms of PTA remain a topic for interdisciplinary investigation. The aim of the present study was to determine the possible cytotoxic effect of 24 h of PTA exposure in Crandall feline kidney (CrFK) and human gastric cells (the HGC-27 cell line) using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and lactose dehydrogenase (LDH) analysis. The cytotoxic effects of PTA (0.0005-500 µg/ml) were found to increase in a dose-dependent manner, whereby the half maximal inhibitory concentration values were 11.17 and 11.86 µg/ml in the CrFK cells, and 2.03 and 2.56 µg/ml in the HGC-27 cells, by LDH and MTT assay, respectively. The results of the present study are consistent with those of previous studies associated with the cytotoxicity of PTA; however, cytotoxicity was identified to occur at significantly lower doses. This cytotoxic effect in vitro at particularly high doses may be linked to the initiation of carcinogenesis as a result of oxidative stress.
Reduced Pteridine Derivatives Induce Apoptosis in Human Neuronal NT2/HNT Cells
Immunobiology, 2000
Elevated concentrations of the pteridine compound neopterin, usually accompanied by 7,8dihydroneopterin were found in cerebrospinal fluids of patients with neurodegenerative diseases and central nervous system infections. Here, the potential of pteridines to induce apoptosis of the human neuronal cell line (NT2) was investigated. Reduced neopterin, biopterin-and folate derivatives led to a time-dependent increase of apoptosis of cells. In contrast, non-reduced pteridines did not significantly alter cell survival. After differentiation of neuronal precursor cells to neurons and astrocyte-like cells, similar effects were detected. Antioxidants partly protected NT2 from pteridines-induced apoptosis, suggesting the involvement of reactive oxygen intermediates. In vitro experiments using dichlorofluorescin-diacetate further indicated a direct formation of reactive oxygen species in cells. Results implicate that high concentrations of reduced pteridines, might contribute to the loss of neuronal cells in neurodegenerative diseases. Abbreviations: IFN-y =interferon-y; GTP =guanosine triphosphate; H 2 0 2 =hydrogen peroxide.
Phytotherapy research : PTR, 2018
Phytochemical investigation of Pogonopus tubulosus trunk led to the isolation of isotubulosine and alangiside, tetrahydroisoquinoline indolic monoterpene alkaloids reported here for the first time for the family Rubiaceae and the genus Pogonopus, respectively. Isotubulosine proved cytotoxic against MCF-7, PC-3, 786-0, HT-29, and HL-60 human cancer cell lines, with GI 50 values ranging from 5.26 to 20.61 μM, in addition to causing G2/M arrest, possibly by inhibiting DNA topoisomerase IIα. Alangiside showed weak cytotoxicity against MCF-7 and HL-60 and proved inactive against PC-3, HT-29, and 786-0 cell lines, with no sign of apoptosis. The alkaloid structures were established on the basis of 1D-and/or 2D-NMR, optical rotation, and HR ESIMS data. Complete 1 H NMR assignments of isotubulosine were also performed, using 1 H-1 H COSY, HSQC, HMBC, NOESY, and 1 H J-resolved techniques and employing experimental and calculated values of homonuclear coupling constants based on the lowest energy conformations. The foregoing results provide new information on the cytotoxicity and mechanism of action of tetrahydroisoquinoline indole monoterpene-type alkaloids and reveal isotubulosine to merit further studies as a potential anticancer agent.
Journal of Oral Pathology & Medicine, 2008
Background: Bracken fern (Pteridium aquilinum) has been consumed by humans and animals for centuries. However, its consumption is associated with a high incidence of cancer in the upper digestory tract of different species. Although the oral cavity is the first site of contact with ingested toxic substances, the interaction of bracken fern composites with oral cell lines has not yet been studied.Methods: In order to study the biological responses of oral cells exposed to bracken fern, we evaluated the genotoxic and cytotoxic effects of a bracken fern aqueous extract in oral cell lines. Human submandibular gland (HSG) and human oral epithelium cells (OSCC-3) cells were treated with three different concentrations of the extract. DNA damage was determined by the comet assay, and cellular morphology was examined by light microscopy. Apoptotic changes were evaluated by transmission electron microscopy and TUNEL assay.Results: The comet assay revealed that the extract was genotoxic for both cell lines but the results were not dose-dependent. The morphological and ultrastructural analyses showed that the extract caused conspicuous alterations in both cell types: uncommon chromatin condensation, nuclear picnosis, cellular volume decrease, nuclear envelope disruption, formation of numerous vacuoles of different sizes and apoptotic bodies. The TUNEL assay confirmed apoptosis induction.Conclusions: These results demonstrate that the extract was cytotoxic to HSG and OSCC-3 cells, and that cellular degeneration occurred mainly by apoptosis. We believe that oral cells could trigger apoptosis after bracken fern induced DNA damage, in order to avoid the malignant transformation.
Journal of Oral Pathology & Medicine, 2008
BACKGROUND: Bracken fern (Pteridium aquilinum) has been consumed by humans and animals for centuries. However, its consumption is associated with a high incidence of cancer in the upper digestory tract of different species. Although the oral cavity is the first site of contact with ingested toxic substances, the interaction of bracken fern composites with oral cell lines has not yet been studied. METHODS: In order to study the biological responses of oral cells exposed to bracken fern, we evaluated the genotoxic and cytotoxic effects of a bracken fern aqueous extract in oral cell lines. Human submandibular gland (HSG) and human oral epithelium cells (OSCC-3) cells were treated with three different concentrations of the extract. DNA damage was determined by the comet assay, and cellular morphology was examined by light microscopy. Apoptotic changes were evaluated by transmission electron microscopy and TUNEL assay. RESULTS: The comet assay revealed that the extract was genotoxic for both cell lines but the results were not dose-dependent. The morphological and ultrastructural analyses showed that the extract caused conspicuous alterations in both cell types: uncommon chromatin condensation, nuclear picnosis, cellular volume decrease, nuclear envelope disruption, formation of numerous vacuoles of different sizes and apoptotic bodies. The TUNEL assay confirmed apoptosis induction. CONCLUSIONS: These results demonstrate that the extract was cytotoxic to HSG and OSCC-3 cells, and that cellular degeneration occurred mainly by apoptosis. We believe that oral cells could trigger apoptosis after bracken fern induced DNA damage, in order to avoid the malignant transformation.
Determination of Ptaquiloside in Pteridium Aquilinum (L.) Kuhn from Central Rhodopes (Bulgaria)
Comptes rendus de l'Académie bulgare des sciences: sciences mathématiques et naturelles
Ptaquiloside, a carcinogenic nor-sesquiterpene glucoside found in bracken (Pteridium aquilinum) is considered to cause tumours in farm animals as well as in humans. Herein we reported the isolation of ptaquiloside from P. aquilinum of Bulgarian origin and its quantitative determination in different plant parts of bracken by its transformation to more stable pterosin B. The studied taxon was characterized by relatively low concentrations of ptaquiloside. The content in the leaf segments, petioles and rhizomes-roots was found to be 0.503±0.043, 0.172 ± 0.018 and 0.059 ± 0.001 mg/g DM respectively.