RESUMO
Excavatolide C (EXCC), a marine coral-derived compound, exhibits an antiproliferation effect on bladder cancer cells. The present study evaluated the improvement in the antiproliferation ability of EXCC by co-treatment with cisplatin in bladder cancer cells. EXCC/cisplatin (12.5 and 1 µg/mL) showed higher antiproliferation effects on bladder cancer cells than single treatments (EXCC or cisplatin alone) in the 48 h ATP assay. EXCC/cisplatin also enhanced the increase in subG1, annexin V-mediated apoptosis, and activation of poly (ADP-ribose) polymerase (PARP) and several caspases (caspases 3, 8, and 9) compared to the single treatments. Cellular and mitochondrial oxidative stress was enhanced with EXCC/cisplatin compared to the single treatments according to analyses of reactive oxygen species (ROS), mitochondrial superoxide, and mitochondrial membrane potential; in addition, cellular antioxidants, such as glutathione (GSH), and the mRNA expressions of antioxidant signaling genes (catalase and NFE2-like bZIP transcription factor 2) were downregulated. EXCC/cisplatin treatment produced more DNA damage than the single treatments, as indicated by γH2AX and 8-hydroxy-2'-deoxyguanosine levels. Moreover, several DNA repair genes for homologous recombination (HR) and non-homologous end joining (NHEJ) were downregulated in EXCC/cisplatin compared to others. The addition of the GSH precursor N-acetylcysteine, which has ROS scavenging activity, attenuated all EXCC/cisplatin-induced changes. Notably, EXCC/cisplatin showed lower antiproliferation, apoptosis, ROS induction, GSH depletion, and γH2AX DNA damage in normal cells than in bladder cancer cells. Therefore, the co-treatment of EXCC/cisplatin reduces the proliferation of bladder cancer cells via oxidative stress-mediated mechanisms with normal cell safety.
Assuntos
Cisplatino , Neoplasias da Bexiga Urinária , Humanos , Espécies Reativas de Oxigênio/metabolismo , Cisplatino/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Apoptose , Antioxidantes/farmacologia , Dano ao DNA , Caspases/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Poli(ADP-Ribose) Polimerases/farmacologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genéticaRESUMO
Antioral cancer drugs need a greater antiproliferative impact on cancer than on normal cells. Demethoxymurrapanine (DEMU) inhibits proliferation in several cancer cells, but an in-depth investigation was necessary. This study evaluated the proliferation-modulating effects of DEMU, focusing on oral cancer and normal cells. DEMU (0, 2, 3, and 4 µg/mL) at 48 h treatments inhibited the proliferation of oral cancer cells (the cell viability (%) for Ca9-22 cells was 100.0 ± 2.2, 75.4 ± 5.6, 26.0 ± 3.8, and 15.4 ± 1.4, and for CAL 27 cells was 100.0 ± 9.4, 77.2 ± 5.9, 57.4 ± 10.7, and 27.1 ± 1.1) more strongly than that of normal cells (the cell viability (%) for S-G cells was 100.0 ± 6.6, 91.0 ± 4.6, 95.0 ± 2.6, and 95.8 ± 5.5), although this was blocked by the antioxidant N-acetylcysteine. The presence of oxidative stress was evidenced by the increase of reactive oxygen species and mitochondrial superoxide and the downregulation of the cellular antioxidant glutathione in oral cancer cells, but these changes were minor in normal cells. DEMU also caused greater induction of the subG1 phase, extrinsic and intrinsic apoptosis (annexin V and caspases 3, 8, and 9), and DNA damage (γH2AX and 8-hydroxy-2-deoxyguanosine) in oral cancer than in normal cells. N-acetylcysteine attenuated all these DEMU-induced changes. Together, these data demonstrate the preferential antiproliferative function of DEMU in oral cancer cells, with the preferential induction of oxidative stress, apoptosis, and DNA damage in these cancer cells, and low cytotoxicity toward normal cells.
Assuntos
Alcaloides , Neoplasias Bucais , Humanos , Antioxidantes/farmacologia , Acetilcisteína/farmacologia , Estresse Oxidativo , Espécies Reativas de Oxigênio , Neoplasias Bucais/tratamento farmacológico , Apoptose , Proliferação de Células , Alcaloides/farmacologia , Alcaloides/uso terapêutico , Indóis/farmacologia , Linhagem Celular Tumoral , Dano ao DNARESUMO
The chemical investigation of a red alga Portieria hornemannii enabled the identification of three new halogenated monoterpenes (1-3) along with two previously identified metabolites (4 and 5). Their structures were determined by spectroscopic analysis and also by utilizing single-crystal diffraction analysis and quantum chemical calculation, as well as by comparison with literature data. Further corrections for dichloro and dibromo carbons using the sorted training set (STS) method were established in this study to significantly improve the accuracy in GIAO 13C NMR calculation of compounds 1-3. To discover the potential bioactive metabolites from P. hornemannii, the anti-inflammatory activities of all compounds were examined. Compounds 1 and 3-5 showed significant anti-inflammatory activity to inhibit the production of pro-inflammatory cytokines in the LPS-stimulated mature dendritic cells.
Assuntos
Anti-Inflamatórios , Rodófitas , Anti-Inflamatórios/farmacologia , Carbono , Movimento Celular , Monoterpenos/farmacologiaRESUMO
Dihydroaustrasulfone alcohol (DA), the synthetic precursor of a natural compound (austrasulfone) isolated from the coral species Cladiella australis, has shown cytotoxic effects against cancer cells. However, it is unknown whether DA has antitumor effects on nasopharyngeal carcinoma (NPC). In this study, we determined the antitumor effects of DA and investigated its mechanism of action on human NPC cells. The MTT assay was used to determine the cytotoxic effect of DA. Subsequently, apoptosis and reactive oxygen species (ROS) analyses were performed by using flow cytometry. Apoptotic and PI3K/AKT pathway-related protein expression was determined using Western blotting. We found that DA significantly reduced the viability of NPC-39 cells and determined that apoptosis was involved in DA-induced cell death. The activity of caspase-9, caspase-8, caspase-3, and PARP induced by DA suggested caspase-mediated apoptosis in DA-treated NPC-39 cells. Apoptosis-associated proteins (DR4, DR5, FAS) in extrinsic pathways were also elevated by DA. The enhanced expression of proapoptotic Bax and decreased expression of antiapoptotic BCL-2 suggested that DA mediated mitochondrial apoptosis. DA reduced the expression of pPI3K and p-AKT in NPC-39 cells. DA also reduced apoptosis after introducing an active AKT cDNA, indicating that DA could block the PI3K/AKT pathway from being activated. DA increased intracellular ROS, but N-acetylcysteine (NAC), a ROS scavenger, reduced DA-induced cytotoxicity. NAC also reversed the chances in pPI3K/AKT expression and reduced DA-induced apoptosis. These findings suggest that ROS-mediates DA-induced apoptosis and PI3K/AKT signaling inactivation in human NPC cells.
RESUMO
Chemical composition screening of an octocoral identified as Sinularia species led to the isolation of a novel diterpenoid, sinulariaone A (1), featuring a 13-membered carbocyclic skeleton. The structure of 1 was established by spectroscopic elucidation, computed calculation, and X-ray diffraction analysis. Moreover, a single-crystal X-ray diffraction analysis of chlorofurancembranoid B (2), obtained in our previous study from the same octocoral species, was reported for the first time to demonstrate the absolute configuration. Diterpenoid 1 showed cytotoxicity towards human promyelocytic leukemia HL-60 cells, with an IC50 value of 38.01 µM.
RESUMO
The Condylactis-genus anemones were examined for their proteinaceous poisons over 50 years ago. On the other hand, the current research focuses on isolating and describing the non-proteinaceous secondary metabolites from the invasive Condylactis anemones, which help take advantage of their population outbreak as a new source of chemical candidates and potential drug leads. From an organic extract of Condylactis sp., a 1,2,4-thiadiazole-based alkaloid, identified as 3,5-bis(3-pyridinyl)-1,2,4-thiadiazole (1), was found to be a new natural alkaloid despite being previously synthesized. The full assignment of NMR data of compound 1, based on the analysis of 2D NMR correlations, is reported herein for the first time. The proposed biosynthetic precursor thionicotinamide (2) was also isolated for the first time from nature along with nicotinamide (3), uridine (5), hypoxanthine (6), and four 5,8-epidioxysteroids (7-10). A major secondary metabolite (-)-betonicine (4) was isolated from Condylactis sp. and found for the first time in marine invertebrates. The four 5,8-epidioxysteroids, among other metabolites, exhibited cytotoxicity (IC50 3.5-9.0 µg/mL) toward five cancer cell lines.
RESUMO
An investigation of the chemical composition of a Formosan soft coral Cespitularia sp. led to the discovery of one new verticillene-type diterpenoid, cespitulactam M (1); one new eudesmane sesquiterpenoid, cespilamide F (2); and three new hydroperoxysteroids (3-5) along with twelve known analogous metabolites (6-17). In addition, one new derivative, cespitulactam M-6,2'-diacetate (1a), was prepared from compound 1. The structures were determined by detailed spectroscopic analyses, particularly HRESIMS and NMR techniques. Moreover, the in vitro cytotoxicity, anti-inflammatory, and antibacterial activity of 1-17 and 1a were evaluated.
Assuntos
Antozoários , Diterpenos , Sesquiterpenos de Eudesmano , Sesquiterpenos , Animais , Antozoários/química , Sesquiterpenos de Eudesmano/química , Espectroscopia de Ressonância Magnética , Diterpenos/química , Sesquiterpenos/química , Estrutura MolecularRESUMO
The present chemical investigation on the organic extract of the soft coral Sarcophyton cinereum has contributed to the isolation of four new cembranoids: 16ß- and 16α-hydroperoxyisosarcophytoxides (1 and 2), 16ß- and 16α-methoxyisosarcophytoxides (3 and 4), and a known cembranoid, lobocrasol (5). The structures of all isolates were elucidated by detailed spectroscopic analysis. Their structures were characterized by a 2,5-dihydrofuran moiety, of which the relative configuration was determined by DU8-based calculation for long-range coupling constants (4JH,H). The cytotoxicity and immunosuppressive activities of all isolates were evaluated in this study.
Assuntos
Antozoários , Diterpenos , Animais , Antozoários/química , Diterpenos/química , Estrutura MolecularRESUMO
Continuing chemical investigation of the Red Sea sponge Spongia sp. led to the isolation of four new 3,4-seco-3,19-dinorspongian diterpenoid lactones, secodinorspongins A-D (1-4), along with a classical spongian diterpenoid lactone, sponginolide (5). The chemical structures, including the absolute configurations of these compounds, were elucidated using the extensive spectroscopic study composed of 1D and 2D NMR data analyses, and a comparison between calculated-electronic-circular-dichroism (ECD) and experimental-circular-dichroism (CD) spectra. A plausible biosynthetic pathway of 1-4 was also proposed. Furthermore, the cytotoxicity, antibacterial and anti-inflammatory activities of 1-5 were evaluated. Compound 1 was found to exhibit inhibitory activity against the growth of Staphylococcus aureus (S. aureus), and 4 and 5 exhibited suppression of superoxide-anion generation and elastase release in fMLF/CB-induced human neutrophils.
Assuntos
Diterpenos , Poríferos , Animais , Humanos , Lactonas , Staphylococcus aureus , Estrutura Molecular , Poríferos/química , Diterpenos/químicaRESUMO
The edible fungus Tremella fuciformis was shown to have a high molecular weight (1.87 × 103 kDa) bioactive polysaccharide, denoted as TFP-F1. Monosaccharide composition and NMR analysis of the polysaccharide and its derivatives indicated it contained fucose (Fucp), xylose (Xylp), mannose (Manp), and glucuronic acid (GlcAp) in a ratio of 0.9:1.0:3.2:1.2. Using IR, NMR, and GC-MS spectroscopic data, the structure of TFP-F1 was elucidated as {â3)-[ß-D-GlcAp-(1â2)]-α-D-Manp-(1â3)-α-D-Manp-(1â3)-[α-L-Fucp-(1â2)-ß-D-Xylp-(1â2)]-α-D-Manp-(1â}n, with partial acetylation of C6-OH in mannoses. Furthermore, at a concentration of 1 µg/mL, TFP-F1 was found to stimulate the secretion of TNF-α and IL-6 in J774A.1 macrophage cells in vitro via interaction with toll-like receptor 4 (TLR4). The removal of O-acetyl groups led to the loss of immunomodulatory activities, demonstrating that O-acetyl groups play an essential role in enhancing the production of pro-inflammatory cytokines.
Assuntos
Receptor 4 Toll-Like , Fator de Necrose Tumoral alfa , Acetilação , Basidiomycota , Citocinas , Carboidratos da Dieta , Fucose , Ácido Glucurônico , Imunomodulação , Interleucina-6 , Manose , Monossacarídeos , Polissacarídeos/química , Polissacarídeos/farmacologia , XiloseRESUMO
Three new 5,5,6,6,5-pentacyclic spongian diterpenes, spongenolactones A-C (1-3), were isolated from a Red Sea sponge Spongia sp. The structures of the new metabolites were elucidated by extensive spectroscopic analysis and the absolute configurations of 1-3 were determined on the basis of comparison of the experimental circular dichroism (CD) and calculated electronic circular dichroism (ECD) spectra. Compounds 1-3 are the first 5,5,6,6,5-pentacyclic spongian diterpenes bearing an ß-hydroxy group at C-1. These metabolites were assayed for their cytotoxic, antibacterial, and anti-inflammatory activities. All three compounds were found to exert inhibitory activity against superoxide anion generation in fMLF/CB-stimulated human neutrophils. Furthermore, 1 showed a higher activity against the growth of Staphylococcus aureus in comparison to 2.
Assuntos
Diterpenos , Poríferos , Animais , Diterpenos/química , Humanos , Oceano Índico , Estrutura Molecular , Staphylococcus aureusRESUMO
Excavatolide C (EXCC) is a bioactive compound derived from the gorgonian octocoral Briareum excavatum, and its anticancer effects are rarely addressed, particularly for bladder cancer. This investigation aimed to explore the potential impacts of EXCC on inhibiting the proliferation of three kinds of bladder cancer cells (5637, BFTC905, and T24). EXCC inhibits bladder cancer cell proliferation based on 48 h ATP assay. This antiproliferation function is validated to be oxidative stress dependent. Cellular and mitochondrial oxidative stresses were upregulated by EXCC, accompanied by depleting glutathione and mitochondrial membrane potential. These antiproliferation and oxidative stress events were suppressed by N-acetylcysteine (NAC), indicating that EXCC has an oxidative stress-regulating function for antiproliferation of bladder cancer cells. Oxidative stress-related responses such as apoptosis, caspase activation, and DNA damage were upregulated by EXCC and reverted by NAC. Taken together, the antiproliferation function of EXCC provides a potential treatment against bladder cancer cells via oxidative stress modulation.
RESUMO
Fucoidan is a dietary brown algae-derived fucose-rich polysaccharide. However, the anticancer effects of fucoidan for oral cancer treatment remain unclear, particularly in terms of its preferential antiproliferation ability and oxidative-stress-associated responses. This study first evaluated the effects and mechanisms of the preferential antiproliferation of fucoidan between oral cancer and non-malignant oral cells (S-G). In a 48 h MTS assay, fucoidan showed higher antiproliferation in response to five types of oral cancer cells, but not S-G cells, demonstrating preferential antiproliferation of oral cancer cells. Oral cancer cells (Ca9-22 and CAL 27) showing high sensitivity to fucoidan were selected to explore the antiproliferation mechanism compared to S-G cells. Fucoidan showed subG1 accumulation and an annexin V increase in apoptosis, accompanied by caspase 8, 9, and 3 activations in oral cancer cells, but not in S-G cells. Fucoidan increased reactive oxygen species and mitochondrial superoxide levels and decreased cellular glutathione in oral cancer cells compared with S-G cells. These oxidative stress effects were attributed to the downregulation of antioxidant signaling genes (NRF2, TXN, and HMOX1) in oral cancer cells rather than S-G cells. Fucoidan showed DNA damage-inducible effects (γH2AX and 8-hydroxy-2-deoxyguanosine) in oral cancer cells but not in S-G cells. Accordingly, these preferential changes in oral cancer but not in non-malignant cells contribute to the preferential antiproliferation mechanism of fucoidan. Furthermore, these changes were reverted by pretreatment with the antioxidant N-acetylcysteine. Therefore, for the first time, this study provides a detailed understanding of the preferential antiproliferation effects and mechanisms of fucoidan in oral cancer cells.
RESUMO
A persistent study on soft coral Sarcophyton tortuosum resulted in the characterization of two new cembranolides, tortuolides A and B (1 and 2), and a new related diterpene, epi-sarcophytonolide Q. Their structures were determined not only by extensive spectroscopic analysis but also by DFT calculations of ECD and NMR data, the latter of which was combined with statistical analysis methods, e.g., DP4+ and J-DP4 approaches. Anti-inflammatory and cytotoxicity activities were evaluated in this study.
Assuntos
Antozoários , Diterpenos , Animais , Antozoários/química , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Diterpenos/química , Diterpenos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Espectroscopia de Ressonância MagnéticaRESUMO
A polyoxygenated and halogenated labdane, spongianol (1); a polyoxygenated steroid, 3ß,5α,9α-trihydroxy-24S-ethylcholest-7-en-6-one (2); a rare seven-membered lactone B ring, (22E,24S)-ergosta-7,22-dien-3ß,5α-diol-6,5-olide (3); and an α,ß-unsaturated fatty acid, (Z)-3-methyl-9-oxodec-2-enoic acid (4) as well as five known compounds, 10-hydroxykahukuene B (5), pacifenol (6), dysidamide (7), 7,7,7-trichloro-3-hydroxy-2,2,6-trimethyl-4-(4,4,4-trichloro-3-methyl-1-oxobu-tylamino)-heptanoic acid methyl ester (8), and the primary metabolite 2'-deoxynucleoside thymidine (9), have been isolated from the Red Sea sponge Spongia sp. The stereoisomer of 3 was discovered in Ganoderma resinaceum, and metabolites 5 and 6, isolated previously from red algae, were characterized unprecedentedly in the sponge. Compounds 7 and 8 have not been found before in the genus Spongia. Compounds 1-9 were also assayed for cytotoxicity as well as antibacterial and anti-inflammatory activities.
Assuntos
Poríferos , Animais , Antibacterianos/química , Anti-Inflamatórios/química , Oceano Índico , Estrutura Molecular , Poríferos/química , Esteroides/químicaRESUMO
In an attempt to explore the bioactive metabolites of the soft coral Sarcophyton cinereum, three new cembranolides, cinerenolides A-C (1-3), and 16 known compounds were isolated and identified from the EtOAc extract. The structures of the new cembranolides were elucidated on the basis of spectroscopic analysis, and the NOE analysis of cinerenolide A (1) was performed with the assistance of the calculated lowest-energy molecular model. The relative configuration of cinerenolide C (3) was determined by the quantum chemical NMR calculation, followed by applying DP4+ analysis. In addition, the cytotoxic assays disclosed that some compounds exhibited moderate to potent activities in the proliferation of P388, DLD-1, HuCCT-1, and CCD966SK cell lines.
Assuntos
Antozoários , Antineoplásicos , Diterpenos , Animais , Antozoários/química , Antineoplásicos/química , Diterpenos/química , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura MolecularRESUMO
Liver cancers, such as hepatocellular carcinoma (HCC), are a highly prevalent cause of cancer-related deaths. Current treatments to combat liver cancer are limited. (-)-Agelasidine A, a compound isolated from the methanol extract of Agelasnakamurai, a sesquiterpene guanidine derived from sea sponge, has antibacterial activity. We demonstrated its anticancer capabilities by researching the associated mechanism of (-)-agelasidine A in human liver cancer cells. We found that (-)-agelasidine A significantly reduced viability in Hep3B and HepG2 cells, and we determined that apoptosis was involved in the (-)-agelasidine A-induced Hep3B cell deaths. (-)-Agelasidine A activated caspases 9, 8, and 3, as well as PARP. This effect was reversed by caspase inhibitors, suggesting caspase-mediated apoptosis in the (-)-agelasidine A-treated Hep3B cells. Moreover, the reduced mitochondrial membrane potential (MMP) and the release of cytochrome c indicated that the (-)-agelasidine A-mediated mitochondrial apoptosis was mechanistic. (-)-Agelasidine A also increased apoptosis-associated proteins (DR4, DR5, FAS), which are related to extrinsic pathways. These events were accompanied by an increase in Bim and Bax, proteins that promote apoptosis, and a decrease in the antiapoptotic protein, Bcl-2. Furthermore, our results presented that (-)-agelasidine A treatment bridged the intrinsic and extrinsic apoptotic pathways. Western blot analysis of Hep3B cells treated with (-)-agelasidine A showed that endoplasmic reticulum (ER) stress-related proteins (GRP78, phosphorylated PERK, phosphorylated eIF2α, ATF4, truncated ATF6, and CHOP) were upregulated. Moreover, 4-PBA, an ER stress inhibitor, could also abrogate (-)-agelasidine A-induced cell viability reduction, annexin V+ apoptosis, death receptor (DR4, DR5, FAS) expression, mitochondrial dysfunction, and cytochrome c release. In conclusion, by activating ER stress, (-)-agelasidine A induced the extrinsic and intrinsic apoptotic pathways of human HCC.
Assuntos
Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Guanidinas/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Sulfonas/farmacologia , Animais , Antineoplásicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Citocromos c/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Guanidinas/isolamento & purificação , Células Hep G2 , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Poríferos/química , Sulfonas/isolamento & purificaçãoRESUMO
Klebsiella pneumoniae serotype KN2 is a carbapenem-resistant strain and leads to the health care-associated infections, such as bloodstream infections. Its capsular polysaccharide (CPS) was isolated and cleaved by a specific enzyme from a bacteriophage into a hexasaccharide-repeating unit. With GC-MS, NMR, and Mass analyses, the structure of KN2 CPS was determined to be {â3)-ß-D-Glcp-(1â3)-[α-D-GlcpA-(1â4)-ß-D-Glcp-(1â6)]-α-D-Galp-(1â6)-ß-D-Galp-(1â3)-ß-D-Galp-(1â}n. We demonstrated that 1 µg/mL CPS could stimulate J774A.1 murine macrophages to release tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in vitro. Also, we proved that KN2 CPS induced the immune response through Toll-like receptor 4 (TLR4) in the human embryonic kidney (HEK)-293 cells. Strikingly, the hexasaccharide alone shows the same immune response as the CPS, suggesting that the hexasaccharide can shape the adaptive immunity to be a potential vaccine adjuvant. The glucuronic acid (GlcA) on other polysaccharides can affect the immune response, but the GlcA-reduced KN2 CPS and hexasaccharide still maintain their immunomodulatory activities.
Assuntos
Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Fatores Imunológicos/farmacologia , Klebsiella pneumoniae/efeitos dos fármacos , Polissacarídeos Bacterianos/farmacologia , Receptor 4 Toll-Like/imunologia , Antibacterianos/química , Carbapenêmicos/química , Células HEK293 , Humanos , Fatores Imunológicos/química , Ligantes , Testes de Sensibilidade Microbiana , Polissacarídeos Bacterianos/químicaRESUMO
Chemical investigation of the soft coral Cespitularia sp. led to the discovery of twelve new verticillane-type diterpenes and norditerpenes: cespitulins H-O (1-8), one cyclic diterpenoidal amide cespitulactam L (9), norditerpenes cespitulin P (10), cespitulins Q and R (11 and 12), four new sesquiterpenes: cespilins A-C (13-15) and cespitulolide (16), along with twelve known metabolites. The structures of these metabolites were established by extensive spectroscopic analyses, including 2D NMR experiments. Anti-inflammatory effects of the isolated compounds were studied by evaluating the suppression of pro-inflammatory protein tumor necrosis factor-α (TNF-α) and nitric oxide (NO) overproduction, and the inhibition of the gene expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in lipopolysaccharide-induced dendritic cells. A number of these metabolites were found to exhibit promising anti-inflammatory activities.
RESUMO
Pancreatic ductal adenocarcinoma is one of the most lethal malignancies: more than half of patients are diagnosed with a metastatic disease, which is associated with a five-year survival rate of only 3%. 5-epi-Sinuleptolide, a norditerpene isolated from Sinularia sp., has been demonstrated to possess cytotoxic activity against cancer cells. However, the cytotoxicity against pancreatic cancer cells and the related mechanisms are unknown. The aim of this study was to evaluate the anti-pancreatic cancer potential of 5-epi-sinuleptolide and to elucidate the underlying mechanisms. The inhibitory effects of 5-epi-sinuleptolide treatment on the proliferation of pancreatic cancer cells were determined and the results showed that 5-epi-sinuleptolide treatment inhibited cell proliferation, induced apoptosis and G2/M cell cycle arrest, and suppressed the invasion of pancreatic cancer cells. The results of western blotting further revealed that 5-epi-sinuleptolide could inhibit JAK2/STAT3, AKT, and ERK phosphorylation, which may account for the diverse cytotoxic effects of 5-epi-sinuleptolide. Taken together, our present investigation unveils a new therapeutic and anti-metastatic potential of 5-epi-sinuleptolide for pancreatic cancer treatment.