Pancracine, a montanine-type Amaryllidaceae alkaloid (AA), is one of the most potent compounds among natural isoquinolines. In previous studies, pancracine exhibited cytotoxic activity against diverse human cancer cell lines in vitro. However, further insight into the molecular mechanisms that underlie the cytotoxic effect of pancracine have not been reported and remain unknown. To fill this void, the cell proliferation and viability of cancer cells was explored using the Trypan Blue assay or by using the xCELLigence system. The impact on the cell cycle was determined by flow cytometry. Apoptosis was evaluated by Annexin V/PI and by quantifying the activity of caspases (-3/7, -8, and -9). Proteins triggering growth arrest or apoptosis were detected by Western blotting. Pancracine has strong antiproliferative activity on A549 cells, lasting up to 96 h, and antiproliferative and cytotoxic effects on MOLT-4 cells. The apoptosis-inducing activity of pancracine in MOLT-4 cells was evidenced by the significantly higher activity of caspases. This was transmitted through the upregulation of p53 phosphorylated on Ser392, p38 MAPK phosphorylated on Thr180/Tyr182, and upregulation of p27. The pancracine treatment negatively altered the proliferation of A549 cells as a consequence of an increase in G1-phase accumulation, associated with the downregulation of Rb phosphorylated on Ser807/811 and with the concomitant upregulation of p27 and downregulation of Akt phosphorylated on Thr308. This was the first study to glean a deeper mechanistic understanding of pancracine activity in vitro. Perturbation of the cell cycle and induction of apoptotic cell death were considered key mechanisms of pancracine action.

• MeSH
• adenokarcinom plic patologie   MeSH
• alkaloidy izolace a purifikace   farmakologie   MeSH
• Amaryllidaceae chemie   MeSH
• antitumorózní látky fytogenní izolace a purifikace   farmakologie   MeSH
• apoptóza účinky léků   MeSH
• buňky A549 MeSH
• buňky Hep G2 MeSH
• heterocyklické sloučeniny tetra- a více cyklické izolace a purifikace   farmakologie   MeSH
• leukemie patologie   MeSH
• lidé MeSH
• MFC-7 buňky MeSH
• nádorové buněčné linie MeSH
• nádory plic patologie   MeSH
• proliferace buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Prenylated or geranylated flavonoids have been studied for their promising antiproliferative and cytotoxic activities. Twelve natural geranylated flavonoids (1-12) were isolated from the fruit of Paulownia tomentosa Steud. Their structures were elucidated using UV and IR spectroscopy, mass spectrometry, and 1D and 2D NMR spectroscopy. The absolute configurations were determined using NMR and circular dichroism. Seven of the compounds were characterized as new geranylated derivatives isolated from a natural source for the first time, namely 3'-O-methyl-5'-hydroxyisodiplacone (3), paulodiplacone A (5), tomentone II (6), tomentone B (7), tomentodiplacone P (8), paulodiplacone B (9), and tomentoflavone A (12). After 24 h of incubation at concentrations in the range 1-30 μM, the isolated compounds were tested for their antiproliferative and cytotoxic potentials against the human monocytic leukaemia cell line THP-1, using WST-1 and LDH assays, respectively. Almost all of the test compounds induced a concentration-dependent reduction in the metabolic activity of THP-1 cells and a concentration-dependent reduction in the cell viability. Diplacone (1) was the most potent antiproliferative and cytotoxic agent (IC50 9.31 ± 0.72 μM, LC50 18.01 ± 1.19 μM). 3'-O-Methyl-5'-hydroxydiplacone (2) showed relatively strong antiproliferative effect (IC50 12.61 ± 0.90 μM) and weaker cytotoxic activity (LC50 > 30 μM), indicating that it may serve as a potential lead compound for further testing. The structure-activity relationship for the 12 isolated compounds is discussed.

• MeSH
• antitumorózní látky fytogenní chemie   izolace a purifikace   farmakologie   MeSH
• flavonoidy chemie   izolace a purifikace   farmakologie   MeSH
• léky antitumorózní - screeningové testy MeSH
• lidé MeSH
• Magnoliopsida chemie   MeSH
• molekulární struktura MeSH
• nádorové buňky kultivované MeSH
• ovoce chemie   MeSH
• proliferace buněk účinky léků   MeSH
• rostlinné extrakty chemie   izolace a purifikace   farmakologie   MeSH
• viabilita buněk účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

In spite of the impressing cytotoxicity of thapsigargin (Tg), this compound cannot be used as a chemotherapeutic drug because of general toxicity, causing unacceptable side effects. Instead, a prodrug targeted towards tumors, mipsagargin, was brought into clinical trials. What substantially reduces the clinical potential is the limited access to Tg and its derivatives and cost-inefficient syntheses with unacceptably low yields. Laser trilobum, which contains a structurally related sesquiterpene lactone, trilobolide (Tb), is successfully cultivated. Here, we report scalable isolation of Tb from L. trilobum and a transformation of Tb to 8-O-(12-aminododecanoyl)-8-O-debutanoylthapsigargin in seven steps. The use of cultivated L. trilobum offers an unlimited source of the active principle in mipsagargin.

• MeSH
• antitumorózní látky fytogenní chemie   izolace a purifikace   MeSH
• Apiaceae chemie   metabolismus   MeSH
• butyráty chemie   izolace a purifikace   MeSH
• furany chemie   izolace a purifikace   MeSH
• lidé MeSH
• molekulární struktura MeSH
• nádory farmakoterapie   patologie   MeSH
• ovoce chemie   metabolismus   MeSH
• oxid uhličitý chemie   MeSH
• rostlinné extrakty chemie   MeSH
• sarkoplazmatická Ca2+-ATPáza antagonisté a inhibitory   metabolismus   MeSH
• superkritická fluidní chromatografie metody   MeSH
• techniky syntetické chemie * MeSH
• thapsigargin analogy a deriváty   izolace a purifikace   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Seven previously undescribed sesquiterpene lactones, three known sesquiterpene lactones (ixerin D, 15-p-hydroxyphenylacetyllactucin, and 15-p-hydroxyphenylacetyllactucin-8-sulfate), and two known quinic acid derivatives (3-O-feruloylquinic acid and 3,5-di-O-caffeoylquinic acid) were isolated from Sonchus palustris L. roots. Four formerly undescribed compounds were elucidated to be 3β,14-dihydroxycostunolide-3-O-β-D-glucopyranosyl-(2-O-p-hydroxyphenylacetyl)-14-O-p-hydroxyphenylacetate, 15-p-methoxyphenylacetyllactucin, 15-p-methoxyphenylacetyllactucin-8-sulfate, and 8-p-hydroxyphenylacetyllactucin-15-sulfate. Additionally, three undescribed conjugates of lactucin and a eudesmanolide type sesquiterpenic acid, sonchpalustrin, 4″-O-methylsonchpalustrin, and isosonchpalustrin, were characterized. The structures of the newly discovered natural products were elucidated using 1D and 2D NMR spectroscopy and UHPLC-HRMS. 15-p-Hydroxyphenylacetyllactucin and 15-p-methoxyphenylacetyllactucin showed significant in vitro cytotoxicity against CEM and BJ cells with IC50 values ranging from 3.9 to 9.8 μM. Compounds 3 and 4 showed also strong anti-inflammatory activity in vitro.

• MeSH
• antitumorózní látky fytogenní chemie   izolace a purifikace   farmakologie   MeSH
• Asteraceae chemie   MeSH
• fytonutrienty chemie   izolace a purifikace   farmakologie   MeSH
• kultivované buňky MeSH
• laktony chemie   izolace a purifikace   farmakologie   MeSH
• léky antitumorózní - screeningové testy MeSH
• lidé MeSH
• proliferace buněk účinky léků   MeSH
• seskviterpeny chemie   izolace a purifikace   farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Plants of the Amaryllidaceae family are promising therapeutic tools for human diseases and have been used as alternative medicines. The specific secondary metabolites of this plant family, called Amaryllidaceae alkaloids (AA), have attracted considerable attention due to their interesting pharmacological activities. One of them, galantamine, is already used in the therapy of Alzheimer's disease as a long acting, selective, reversible inhibitor of acetylcholinesterase. One group of AA is the montanine-type, such as montanine, pancracine and others, which share a 5,11-methanomorphanthridine core. So far, only 14 montanine-type alkaloids have been isolated. Compared with other structural-types of AA, montanine-type alkaloids are predominantly present in plants in low concentrations, but some of them display promising biological properties, especially in vitro cytotoxic activity against different cancerous cell lines. The present review aims to summarize comprehensively the research that has been published on the Amaryllidaceae alkaloids of montanine-type.

• MeSH
• alkaloidy amarylkovitých chemie   izolace a purifikace   farmakologie   MeSH
• Amaryllidaceae chemie   metabolismus   MeSH
• antiprotozoální látky chemie   izolace a purifikace   farmakologie   MeSH
• antitumorózní látky fytogenní chemie   izolace a purifikace   farmakologie   MeSH
• cholinesterasové inhibitory chemie   izolace a purifikace   farmakologie   MeSH
• fenantridiny chemie   izolace a purifikace   farmakologie   MeSH
• galantamin chemie   izolace a purifikace   farmakologie   MeSH
• heterocyklické sloučeniny tetra- a více cyklické chemie   izolace a purifikace   farmakologie   MeSH
• inhibiční koncentrace 50 MeSH
• isochinoliny chemie   izolace a purifikace   farmakologie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nootropní látky chemie   izolace a purifikace   farmakologie   MeSH
• rostlinné extrakty chemie   MeSH
• sekundární metabolismus MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Bersavine is the new bisbenzylisoquinoline alkaloid isolated from the Berberis vulgaris L.(Berberidaceae) plant. The results of cytotoxicity screening 48 h post-treatment showed thatbersavine considerably inhibits the proliferation and viability of leukemic (Jurkat, MOLT-4), colon(HT-29), cervix (HeLa) and breast (MCF-7) cancer cells with IC50 values ranging from 8.1 to 11 μM.The viability and proliferation of leukemic Jurkat and MOLT-4 cells were decreased after bersavinetreatment in a time- and dose-dependent manner. Bersavine manifested concentration-dependentantiproliferative activity in human lung, breast, ovarian and hepatocellular carcinoma cell linesusing a xCELLigence assay. Significantly higher percentages of MOLT-4 cells exposed to bersavineat 20 μM for 24 h were arrested in the G1 phase of the cell cycle using the flow cytometry method.The higher percentage of apoptotic cells was measured after 24 h of bersavine treatment. Theupregulation of p53 phosphorylated on Ser392 was detected during the progression of MOLT-4 cellapoptosis. Mechanistically, bersavine-induced apoptosis is an effect of increased activity ofcaspases, while reduced proliferation seems dependent on increased Chk1 Ser345 phosphorylationand decreased Rb Ser807/811 phosphorylation in human leukemic cells.

• MeSH
• alkaloidy * chemie   izolace a purifikace   farmakologie   MeSH
• antitumorózní látky fytogenní * chemie   izolace a purifikace   farmakologie   MeSH
• apoptóza účinky léků   MeSH
• Berberis chemie   MeSH
• buňky Hep G2 MeSH
• buňky HT-29 MeSH
• cytotoxiny * chemie   izolace a purifikace   farmakologie   MeSH
• G1 fáze účinky léků   MeSH
• HeLa buňky MeSH
• Jurkat buňky MeSH
• léky antitumorózní - screeningové testy MeSH
• leukemie farmakoterapie   metabolismus   patologie   MeSH
• lidé MeSH
• MFC-7 buňky MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

This paper describes the synthesis of a new A-homo lactam D-homo lactone androstane derivative from dehydroepiandrosterone. To evaluate the impact of the introduction of nitrogen in the parental scaffold on biological activity, a new androstane enamide-type lactam derivative was prepared and characterized. The new compound as well as starting compounds were screened for cytotoxic, anti-angiogenic and anti-inflammatory activities using several human cancer cell lines (MCF-7, MDA-MB-231, PC3, CEM, G-361, HeLa), endothelial (HUVEC) and non-tumour (MRC-5 and BJ) cell lines. Strong cytotoxic and anti-inflammatory activity with a broad therapeutical window was demonstrated by the A-homo lactam D-homo lactone androstane derivative. The induction of apoptosis in treated PC3 cultures was confirmed using apoptotic morphology screening and a fluorescent double-staining method. New A-homo lactam D-homo lactone androstane derivative induced apoptosis more than the tested reference compounds, Formestane and Doxorubicin. An in silico ADME analysis showed that the compounds possess drug-like properties.

• MeSH
• androstany chemie   izolace a purifikace   farmakologie   MeSH
• antiflogistika chemie   izolace a purifikace   farmakologie   MeSH
• antitumorózní látky fytogenní chemie   izolace a purifikace   farmakologie   MeSH
• apoptóza účinky léků   MeSH
• E-selektin antagonisté a inhibitory   biosyntéza   MeSH
• kultivované buňky MeSH
• laktony chemie   izolace a purifikace   farmakologie   MeSH
• léky antitumorózní - screeningové testy MeSH
• lidé MeSH
• molekulární konformace MeSH
• optické zobrazování MeSH
• proliferace buněk účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Sesquiterpene lactones are bioactive natural compounds with anticancer, antiprotozoal, immunomodulatory, antibacterial and antiviral activity which have potential for drug development. The aim of this review article is to provide a brief insight into the field of sesquiterpene lactones: the main mechanisms of their biological actions, as well as particular compounds, are described, some of which have already become a basis of a drug development and are being tested in clinical trials.

• MeSH
• antitumorózní látky fytogenní izolace a purifikace   MeSH
• artemisininy MeSH
• etnofarmakologie MeSH
• farmakognozie MeSH
• imunomodulace MeSH
• inhibitory enzymů MeSH
• laktony * farmakokinetika   farmakologie   terapeutické užití   MeSH
• seskviterpeny guajanové farmakokinetika   farmakologie   terapeutické užití   MeSH
• seskviterpeny farmakokinetika   farmakologie   terapeutické užití   MeSH
• Tanacetum parthenium chemie   MeSH
• thapsigargin MeSH
• Publikační typ
• práce podpořená grantem MeSH

It is supposed that plant functional foods, rich in phytochemicals, may potentially have preventive effects in carcinogenesis. In this study, the anticancer effects of cloves in the in vivo and in vitro mammary carcinoma model were assessed. Dried flower buds of cloves (CLOs) were used at two concentrations of 0.1% and 1% through diet during 13 weeks after the application of chemocarcinogen. After autopsy, histopathological and immunohistochemical analyses of rat mammary carcinomas were performed. Moreover, in vitro evaluation using MCF-7 cells was carried out. Dietary administered CLO caused the dose-dependent decrease in tumour frequency by 47.5% and 58.5% when compared to control. Analysis of carcinoma cells in animals showed bcl-2, Ki67, VEGFA, CD24 and CD44 expression decrease and Bax, caspase-3 and ALDH1 expression increase after high-dose CLO administration. MDA levels were substantially decreased in rat carcinomas in both CLO groups. The evaluation of histone modifications revealed increase in lysine trimethylations and acetylations (H4K20me3, H4K16ac) in carcinomas after CLO administration. TIMP3 promoter methylation levels of CpG3, CpG4, CpG5 islands were altered in treated cancer cells. An increase in total RASSF1A promoter methylation (three CpG sites) in CLO 1 group was found. In vitro studies showed antiproliferative and pro-apoptotic effects of CLO extract in MCF-7 cells (analyses of cytotoxicity, Brdu, cell cycle, annexin V/PI, caspase-7, Bcl-2 and mitochondrial membrane potential). This study showed a significant anticancer effect of clove buds in the mammary carcinoma model in vivo and in vitro.

• MeSH
• adenokarcinom dietoterapie   genetika   metabolismus   patologie   MeSH
• antigen Ki-67 genetika   metabolismus   MeSH
• antitumorózní látky fytogenní izolace a purifikace   farmakologie   MeSH
• epigeneze genetická účinky léků   MeSH
• experimentální nádory mléčných žláz dietoterapie   genetika   metabolismus   patologie   MeSH
• histony genetika   metabolismus   MeSH
• kaspasa 3 genetika   metabolismus   MeSH
• krysa rodu rattus MeSH
• květy chemie   MeSH
• lidé MeSH
• membránový potenciál mitochondrií účinky léků   MeSH
• metylace DNA účinky léků   MeSH
• MFC-7 buňky MeSH
• nádorové supresorové proteiny genetika   metabolismus   MeSH
• nádory prsu dietoterapie   genetika   metabolismus   patologie   MeSH
• potkani Sprague-Dawley MeSH
• protein X asociovaný s bcl-2 genetika   metabolismus   MeSH
• protoonkogenní proteiny c-bcl-2 genetika   metabolismus   MeSH
• retinaldehydrogenasa genetika   metabolismus   MeSH
• rostlinné extrakty chemie   MeSH
• signální transdukce MeSH
• Syzygium chemie   MeSH
• tumor burden účinky léků   MeSH
• vaskulární endoteliální růstový faktor A genetika   metabolismus   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• antibakteriální látky dějiny   farmakologie   MeSH
• antitumorózní látky fytogenní farmakologie   izolace a purifikace   terapeutické užití   MeSH
• Basidiomycota chemie   imunologie   MeSH
• biotechnologie * MeSH
• Claviceps chemie   patogenita   MeSH
• houby * chemie   klasifikace   MeSH
• imunizace MeSH
• imunosupresiva izolace a purifikace   MeSH
• lidé MeSH
• námelové alkaloidy biosyntéza   chemie   izolace a purifikace   MeSH
• peniciliny biosyntéza   farmakologie   terapeutické užití   MeSH
• statiny chemie   izolace a purifikace   terapeutické užití   MeSH
• Check Tag
• lidé MeSH