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1.
Int J Mol Sci ; 24(6)2023 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-36982818

RESUMEN

Ginger-derived compounds are abundant sources of anticancer natural products. However, the anticancer effects of (E)-3-hydroxy-1-(4'-hydroxy-3',5'-dimethoxyphenyl)-tetradecan-6-en-5-one (3HDT) have not been examined. This study aims to assess the antiproliferation ability of 3HDT on triple-negative breast cancer (TNBC) cells. 3HDT showed dose-responsive antiproliferation for TNBC cells (HCC1937 and Hs578T). Moreover, 3HDT exerted higher antiproliferation and apoptosis on TNBC cells than on normal cells (H184B5F5/M10). By examining reactive oxygen species, mitochondrial membrane potential, and glutathione, we found that 3HDT provided higher inductions for oxidative stress in TNBC cells compared with normal cells. Antiproliferation, oxidative stress, antioxidant signaling, and apoptosis were recovered by N-acetylcysteine, indicating that 3HDT preferentially induced oxidative-stress-mediated antiproliferation in TNBC cells but not in normal cells. Moreover, by examining γH2A histone family member X (γH2AX) and 8-hydroxy-2-deoxyguanosine, we found that 3HDT provided higher inductions for DNA damage, which was also reverted by N-acetylcysteine. In conclusion, 3HDT is an effective anticancer drug with preferential antiproliferation, oxidative stress, apoptosis, and DNA damage effects on TNBC cells.


Asunto(s)
Neoplasias de la Mama Triple Negativas , Zingiber officinale , Humanos , Acetilcisteína/farmacología , Línea Celular Tumoral , Proliferación Celular , Apoptosis , Daño del ADN
2.
Pharmazie ; 74(11): 675-679, 2019 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-31739836

RESUMEN

Docosahexaenoic acid (DHA) is rich in fish oil with many pharmacological impacts such as anti-inflammation and anti-cancer activities. In the present study, we aimed to investigate the inhibitory effects of DHA on the invasion and inflammation in prostate cancer cells. The cytotoxicity of DHA with or without lipopolysaccharides (LPS) treatment was evaluated by MTT assay. The invasion and wound healing assays were used to determine the roles of DHA in cell migration and invasion after LPS treatment. The expression levels of IL-6 and IL-8 were detected using ELISA assay. The protein expression was investigated by Western blotting. DHA exhibited significant cytotoxicity at the concentration of 100 µM in PC3 cells. Exposure to DHA (6, 12 and 25 µM) dose-dependently inhibited invasion and wound closure potential in PC3 cells after LPS treatment. DHA dose-dependently downregulated LPS-induced expression levels of IL-6 and IL-8. In addition, the LPS-induced protein levels of p-AKT and COX-2 were suppressed by DHA treatment. Our results indicate that low doses of DHA effectively inhibit metastasis by decreasing IL-6, IL-8, p-AKT and COX-2 expression levels after LPS treatment.


Asunto(s)
Ácidos Docosahexaenoicos/farmacología , Inflamación/tratamiento farmacológico , Neoplasias de la Próstata/tratamiento farmacológico , Movimiento Celular/efectos de los fármacos , Ácidos Docosahexaenoicos/administración & dosificación , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Inflamación/patología , Lipopolisacáridos , Masculino , Metástasis de la Neoplasia/prevención & control , Células PC-3 , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología
3.
Mar Drugs ; 16(10)2018 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-30332851

RESUMEN

Presently, natural sources and herbs are being sought for the treatment of human oral squamous cell carcinoma (OSCC) in order to alleviate the side effects of chemotherapy. This study investigates the effect of sandensolide, a cembrane isolated from Sinularia flexibilis, to inhibit human OSCC cell growth with the aim of developing a new drug for the treatment of oral cancer. In vitro cultured human OSCC models (Ca9.22, SCC9 and HSC-3 cell lines) and oral normal cells (HGF-1), as well as a zebrafish xenograft model, were used to test the cytotoxicity of sandensolide (MTT assay), as well as to perform cell cycle analysis and Western blotting. Both the in vitro bioassay and the zebrafish xenograft model demonstrated the anti-oral cancer effect of sandensolide. Moreover, sandensolide was able to significantly suppress colony formation and induce apoptosis, as well as cell cycle arrest, in OSCC by regulating multiple key proteins. Induction of reactive oxygen species (ROS) was observed in sandensolide-treated oral cancer cells. However, these apoptotic changes were rescued by NAC pretreatment. These findings contribute to the knowledge of the model of action of sandensolide, which may induce oxidative stress-mediated cell death pathways as a potential agent in oral cancer therapeutics.


Asunto(s)
Antozoos , Antineoplásicos/farmacología , Carcinoma de Células Escamosas/tratamiento farmacológico , Diterpenos/farmacología , Neoplasias de la Boca/tratamiento farmacológico , Acetilcisteína/farmacología , Animales , Antineoplásicos/aislamiento & purificación , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Diterpenos/química , Diterpenos/aislamiento & purificación , Diterpenos/uso terapéutico , Humanos , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , Pez Cebra
4.
Int J Mol Sci ; 19(9)2018 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-30213077

RESUMEN

Toll-like receptors (TLRs) are a well-known family of pattern recognition receptors that play an important role in a host immune system. TLR triggering leads to the induction of pro-inflammatory cytokines and chemokines, driving the activation of both innate and adaptive immunity. Recently, an increasing number studies have shown the link between TLRs and cancer. Among them, the toll-like receptor 4 (TLR4) signaling pathway is associated with inflammatory response and cancer progression. Dietary phytochemicals are potential modulators of immunological status with various pharmacological properties including anti-cancer, anti-oxidant and anti-inflammatory. Curcumin, 6-gingerol, 6-shogaol, 1-dehydro-10-gingerdione, epigallocatechin gallate (EGCG), luteolin, quercetin, resveratrol, caffeic acid phenethyl ester, xanthohumol, genistein, berberine, and sulforaphane can inhibit TLR4 activation. The aim of the present review is to describe the role of the TLR4 signaling pathway between inflammatory response and cancer progression. We further introduce bioactive phytochemicals with potential anti-inflammation and chemoprevention by inhibiting TLR activation.


Asunto(s)
Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Neoplasias/metabolismo , Neoplasias/prevención & control , Fitoquímicos/uso terapéutico , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 4/metabolismo , Animales , Humanos
6.
Molecules ; 23(4)2018 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-29642488

RESUMEN

The natural compound sinularin, isolated from marine soft corals, is antiproliferative against several cancers, but its possible selective killing effect has rarely been investigated. This study investigates the selective killing potential and mechanisms of sinularin-treated breast cancer cells. In 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H- tetrazolium, inner salt (MTS) assay, sinularin dose-responsively decreased the cell viability of two breast cancer (SKBR3 and MDA-MB-231) cells, but showed less effect on breast normal (M10) cells after a 24 h treatment. According to 7-aminoactinomycin D (7AAD) flow cytometry, sinularin dose-responsively induced the G2/M cycle arrest of SKBR3 cells. Sinularin dose-responsively induced apoptosis on SKBR3 cells in terms of a flow cytometry-based annexin V/7AAD assay and pancaspase activity, as well as Western blotting for cleaved forms of poly(ADP-ribose) polymerase (PARP), caspases 3, 8, and 9. These caspases and PARP activations were suppressed by N-acetylcysteine (NAC) pretreatment. Moreover, sinularin dose-responsively induced oxidative stress and DNA damage according to flow cytometry analyses of reactive oxygen species (ROS), mitochondrial membrane potential (MitoMP), mitochondrial superoxide, and 8-oxo-2'-deoxyguanosine (8-oxodG)). In conclusion, sinularin induces selective killing, G2/M arrest, apoptosis, and oxidative DNA damage of breast cancer cells.


Asunto(s)
Antineoplásicos/farmacología , Neoplasias de la Mama/genética , Daño del ADN , Diterpenos/farmacología , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Compuestos Heterocíclicos con 3 Anillos/farmacología , Apoptosis , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Caspasas/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Poli(ADP-Ribosa) Polimerasas/metabolismo
7.
Int Ophthalmol ; 38(2): 747-756, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28393322

RESUMEN

AIM: This study was to investigate the anti-angiogenic effect of hexahydrocurcumin (HHC) to evaluate gene (p-basic fibroblast growth factor (bFGF)-SAINT-18 & p-vascular endothelial growth factor (VEGF)-SAINT-18 complex)-induced corneal neovascularization (CorNV) in rats. METHODS: CorNV was induced in 24 eyes of 24 rats. Four groups (Group A: 0 µg, B: 0.01 µg, C: 0.1 µg, and D: 1 µg) of HHC were prepared and implanted into the rat subconjunctival substantia propria 1.5 mm from the limbus at temporal side. The 1 µg of p-bFGF-SAINT-18 & p-VEGF-SAINT-18 complex were prepared and implanted into the rat corneal stroma 1.5 mm from the limbus at the same side. Inhibition of CorNV was observed and quantified from day 1 to day 60. bFGF and VEGF protein expression were analyzed by biomicroscopic examination, western blot analysis, and immunohistochemistry. RESULTS: Subconjunctival injection by 1 µg HHC successfully inhibited gene-induced CorNV in rats. bFGF and VEGF protein expression were reduced after 6 days. Meanwhile, the reduction of HLA-DR expression was detected. CONCLUSIONS: Our study showed that the HHC might provide an important anti-angiogenesis factor to inhibit CorNV development at the corneal experimental angiogenesis model.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Neovascularización de la Córnea/tratamiento farmacológico , Curcumina/análogos & derivados , Inhibidores de la Angiogénesis/farmacología , Animales , Western Blotting , Conjuntiva/efectos de los fármacos , Conjuntiva/metabolismo , Neovascularización de la Córnea/metabolismo , Curcumina/farmacología , Curcumina/uso terapéutico , Modelos Animales de Enfermedad , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Antígenos HLA-DR/metabolismo , Masculino , Ratas , Ratas Sprague-Dawley , Factor A de Crecimiento Endotelial Vascular/metabolismo
8.
Int J Mol Sci ; 18(11)2017 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-29140298

RESUMEN

The natural pure compound obtusilactone A (OA) was identified in Cinnamomum kotoense Kanehira & Sasaki, and shows effective anti-cancer activity. We studied the effect of OA on osteogenesis of bone marrow-derived mesenchymal stem cells (BMSCs). OA possesses biocompatibility, stimulates Alkaline Phosphatase (ALP) activity and facilitates mineralization of BMSCs. Expression of osteogenesis markers BMP2, Runx2, Collagen I, and Osteocalcin was enhanced in OA-treated BMSCs. An in vivo rat model with local administration of OA via needle implantation to bone marrow-residing BMSCs revealed that OA increased the new bone formation and trabecular bone volume in tibias. Micro-CT images and H&E staining showed more trabecular bone at the needle-implanted site in the OA group than the normal saline group. Thus, OA confers an osteoinductive effect on BMSCs via induction of osteogenic marker gene expression, such as BMP2 and Runx2 expression and subsequently elevates ALP activity and mineralization, followed by enhanced trabecular bone formation in rat tibias. Therefore, OA is a potential osteoinductive drug to stimulate new bone formation by BMSCs.


Asunto(s)
Células de la Médula Ósea/citología , Lignanos/farmacología , Células Madre Mesenquimatosas/citología , Osteogénesis/efectos de los fármacos , Animales , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/metabolismo , Hueso Esponjoso/diagnóstico por imagen , Hueso Esponjoso/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/genética , Cinnamomum/química , Regulación de la Expresión Génica/efectos de los fármacos , Imagenología Tridimensional , Lignanos/química , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Ratones Endogámicos BALB C , Oseointegración/efectos de los fármacos , Oseointegración/genética , Osteogénesis/genética , Ratas Sprague-Dawley , Tibia/efectos de los fármacos , Tibia/crecimiento & desarrollo , Microtomografía por Rayos X
9.
Int J Mol Sci ; 18(12)2017 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-29211014

RESUMEN

Sepsis is an overwhelming systemic response to infection that frequently results in tissue damage, organ failure, and even death. Nitric oxide (NO), prostaglandin E2 (PGE2), and cytokine overproduction are thought to be associated with the immunostimulatory cascade in sepsis. In the present study, we analyzed the anti-inflammatory efficacy of the pheophytin-b on both RAW 264.7 murine macrophage and purified human CD14⁺ monocytes stimulated with lipopolysaccharide (LPS) and elucidated the mechanisms by analyzing the cell signaling pathways known to be activated in sepsis. Pheophytin-b suppressed the overexpression of NO, PGE2, and cytokines in LPS-stimulated macrophages without inducing cytotoxicity. It also reduced NOS2 and COX-2 mRNA and protein levels. The inhibitory effects on NO, PGE2, and cytokine overproduction arose from the suppression of STAT-1 and PI3K/Akt pathways; no changes in NF-κB, MAPK, and AP-1 signaling were detected. Thus, pheophytin-b may represent a potential candidate to beneficially modulate the inflammatory response in sepsis.


Asunto(s)
Antiinflamatorios/farmacología , Citocinas/metabolismo , Dinoprostona/metabolismo , Macrófagos/efectos de los fármacos , Óxido Nítrico/metabolismo , Feofitinas/farmacología , Animales , Línea Celular , Células Cultivadas , Citocinas/genética , Humanos , Lipopolisacáridos/toxicidad , Macrófagos/metabolismo , Ratones , Transducción de Señal
10.
Molecules ; 22(9)2017 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-28872603

RESUMEN

Ginger has many bioactive compounds with pharmacological activities. However, few studies are known about these bioactive compounds activity in chemoresistant cells. The aim of the present study was to investigate the anticancer properties of ginger phytochemicals in docetaxel-resistant human prostate cancer cells in vitro. In this study, we isolated 6-gingerol, 10-gingerol, 4-shogaol, 6-shogaol, 10-shogaol, and 6-dehydrogingerdione from ginger. Further, the antiproliferation activity of these compounds was examined in docetaxel-resistant (PC3R) and sensitive (PC3) human prostate cancer cell lines. 6-gingerol, 10-gingerol, 6-shogaol, and 10-shogaol at the concentration of 100 µM significantly inhibited the proliferation in PC3R but 6-gingerol, 6-shogaol, and 10-shogaol displayed similar activity in PC3. The protein expression of multidrug resistance associated protein 1 (MRP1) and glutathione-S-transferase (GSTπ) is higher in PC3R than in PC3. In summary, we isolated the bioactive compounds from ginger. Our results showed that 6-gingerol, 10-gingerol, 6-shogaol, and 10-shogaol inhibit the proliferation of PC3R cells through the downregulation of MRP1 and GSTπ protein expression.


Asunto(s)
Antineoplásicos/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Fitoquímicos/farmacología , Extractos Vegetales/farmacología , Neoplasias de la Próstata/tratamiento farmacológico , Taxoides/uso terapéutico , Zingiber officinale/química , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Docetaxel , Humanos , Masculino , Fitoquímicos/química , Extractos Vegetales/química
11.
Biochem Biophys Res Commun ; 473(1): 303-310, 2016 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-27016482

RESUMEN

The ROMK1 (Kir1.1) channel activity is predominantly regulated by intracellular pH (pHi) and phosphatidylinositol 4,5-bisphosphate (PIP2). Although several residues were reported to be involved in the regulation of pHi associated with PIP2 interaction, the detailed molecular mechanism remains unclear. We perform experiments in ROMK1 pHi-gating with electrophysiology combined with mutational and structural analysis. In the present study, non basic residues of C-terminal region (S219, N215, I192, L216 and L220) in ROMK1 channels have been found to mediate channel-PIP2 interaction and pHi gating. Further, our structural results show these residues with an appropriate distance to interact with membrane PIP2. Meanwhile, a cluster of basic residues (R188, R217 and K218), which was previously discovered regarding the interaction with PIP2, exists in this appropriate distance to discriminate the regulation of channel-PIP2 interaction and pHi-gating. This appropriate distance can be observed with high conservation in the Kir channel family. Our results provide insight that an appropriate distance cooperates with the electrostatics interaction of channel-PIP2 to regulate pHi-gating.


Asunto(s)
Fosfatidilinositol 4,5-Difosfato/química , Canales de Potasio de Rectificación Interna/fisiología , Algoritmos , Secuencia de Aminoácidos , Animales , Pollos , Electrofisiología , Femenino , Humanos , Concentración de Iones de Hidrógeno , Ratones , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Datos de Secuencia Molecular , Mutación , Oocitos/metabolismo , Canales de Potasio de Rectificación Interna/metabolismo , Estructura Terciaria de Proteína , Homología de Secuencia de Aminoácido , Electricidad Estática , Xenopus laevis
12.
Molecules ; 21(7)2016 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-27409597

RESUMEN

Oxidative stress-mediated cellular injury has been considered as a major cause of neurodegenerative diseases including Alzheimer's and Parkinson's diseases. The scavenging of reactive oxygen species (ROS) mediated by antioxidants may be a potential strategy for retarding the diseases' progression. Costunolide (CS) is a well-known sesquiterpene lactone, used as a popular herbal remedy, which possesses anti-inflammatory and antioxidant activity. This study aimed to investigate the protective role of CS against the cytotoxicity induced by hydrogen peroxide (H2O2) and to elucidate potential protective mechanisms in PC12 cells. The results showed that the treatment of PC12 cells with CS prior to H2O2 exposure effectively increased the cell viability. Furthermore, it decreased the intracellular ROS, stabilized the mitochondria membrane potential (MMP), and reduced apoptosis-related protein such as caspase 3. In addition, CS treatment attenuated the cell injury by H2O2 through the inhibition of phosphorylation of p38 and the extracellular signal-regulated kinase (ERK). These results demonstrated that CS is promising as a potential therapeutic candidate for neurodegenerative diseases resulting from oxidative damage and further research on this topic should be encouraged.


Asunto(s)
Antioxidantes/farmacología , Peróxido de Hidrógeno/toxicidad , Sesquiterpenos/farmacología , Animales , Antioxidantes/química , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Oxidación-Reducción/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Células PC12 , Fosforilación/efectos de los fármacos , Ratas , Especies Reactivas de Oxígeno/metabolismo , Sesquiterpenos/química
13.
Exp Dermatol ; 24(12): 930-5, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26174122

RESUMEN

Melanoma is the deadliest cancer. We identified 7-hydroxydehydronuciferine (7-HDNF) isolated from the leaves of Nelumbo nucifera Gaertn cv. Rosa-plena to be a bio-active agent that antagonizes melanoma tumor growth in mice xenograft model in vivo. Cell proliferation assay demonstrated strong anticancer effects of 7-HDNF to exhibit a dose-dependent behaviour and displayed minor cytotoxicities on normal human skin cells, including epidermal keratinocytes and melanocytes, and dermal fibroblasts. With acridine orange (AO) staining and flow analysis, we found 7-HDNF induced the formation of intracellular vacuoles and the augmentation of acidic vesicular organelles (AVO). The apoptotic cell death ratio was measured via two-dimensional flow cytometry by annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) double stained to confirm the cellular membrane asymmetry lost. One-dimensional flow cytometric analysis showed 7-HDNF increased the cellular arrest in cell cycle at the G2/M phase. Through Western blot examinations, protein expressions were discovered to verify autophagy and apoptosis response mechanisms sharing the associated pathways. Finally, 7-HDNF presented a high-quality antimigratory activity in wound-healing assay. Overall, 7-HDNF presented high-quality anticancer bio-functions and inhibited melanoma tumor growth in vivo and in vitro.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Aporfinas/farmacología , Melanoma/tratamiento farmacológico , Animales , Antineoplásicos Fitogénicos/química , Apoptosis/efectos de los fármacos , Aporfinas/química , Autofagia/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Femenino , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Humanos , Queratinocitos/citología , Queratinocitos/efectos de los fármacos , Medicina Tradicional China , Melanoma/metabolismo , Melanoma/patología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas Mitocondriales/metabolismo , Nelumbo/química , Plantas Medicinales/química , Ensayos Antitumor por Modelo de Xenoinjerto
14.
Molecules ; 20(7): 12166-74, 2015 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-26151114

RESUMEN

Seven compounds were extracted and purified from the roots of Michelia compressa var. lanyuensis. These compounds are liriodenine, (-)-N-acetylanonaine, pressalanine A, p-dihydroxybenzaldehyde, 3,4-dihydroxybenzoic acid, (-)-bornesitol and ß-sitostenone. These compounds were screened for anti-proliferation and anti-tyrosinase activities in B16F10 cells. Liriodenine, pressalanine A, (-)-bornesitol and ß-sitostenone displayed cytotoxicity at high concentration (100 µM), but liriodenine (5 µM), (-)-N-acetylanonaine (10 µM), and ß-sitostenone (5 µM) inhibit tyrosinase activity and reduce the melanin content in B16F10 cells without cytotoxicity, suggesting that liriodenine and ß-sitostenone could be safe and potentially used in cosmetic skin whitening.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Magnoliaceae/química , Melaninas/antagonistas & inhibidores , Extractos Vegetales/farmacología , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Melanoma Experimental/patología , Ratones
15.
Int J Mol Sci ; 15(3): 3624-39, 2014 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-24583851

RESUMEN

Nelumbo nucifera Gaertn. cv. Rosa-plena (Nelumbonaceae), commonly known as lotus, is a perennial aquatic plant grown and consumed throughout Asia. All parts of N. nucifera have been used for various medicinal purposes in oriental medicine. From the leaves of Nelumbo nucifera Gaertn. cv. Rosa-plena (an aquatic plant), liriodenine (1), lysicamine (2), (-)-anonaine (3), (-)-asimilobine (4), (-)-caaverine (5), (-)-N-methylasimilobine (6), (-)-nuciferine (7), (-)-nornuciferine (8), (-)-roemerine (9), 7-hydroxydehydronuciferine (10) and cepharadione B (11) were isolated and identification and anthelmintic activities of aporphine was evaluated against Anisakis simplex and Hymenolepis nana. This study found that the above constituents killed H. nana or reduced their spontaneous movements (oscillation/peristalsis). However, the above constituents at various concentrations demonstrated no larvicidal effect or ability to halt spontaneous parasite movement for 72 h against A. simplex, respectively. In addition, according to an assay of cestocidal activity against H. nana and nematocidal activity against A. simplex, we found that the above compounds showed greater lethal efficacy on H. nana than against A. simplex. Further investigation showed that these above constituents have effects against peroxyl radicals under cestocidal effect. Together, these findings suggest that these constituents of Nelumbo nucifera Gaertn. cv. Rosa-plena might be used as anthelmintic agents against H. nana.


Asunto(s)
Antihelmínticos/farmacología , Aporfinas/farmacología , Hymenolepis nana/efectos de los fármacos , Nelumbo/química , Alcaloides/aislamiento & purificación , Alcaloides/farmacología , Animales , Anisakis/efectos de los fármacos , Anisakis/fisiología , Antihelmínticos/aislamiento & purificación , Aporfinas/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Hymenolepis nana/fisiología , Movimiento/efectos de los fármacos , Hojas de la Planta/química , Factores de Tiempo
16.
Int J Mol Sci ; 15(12): 22819-34, 2014 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-25501336

RESUMEN

Inflammation is a serious health issue worldwide that induces many diseases such as sepsis. There has been a vast search for potentially effective drugs to decrease mortality from sepsis. Pheophytin a is a chlorophyll-related compound derived from green tea. We found that pre-treatment with pheophytin a suppressed lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin E2 (PGE2), and interleukin-1ß in RAW 264.7 macrophages. NO synthase-2 (NOS2) and cyclooxygenase-2 (COX-2) expression levels were repressed by pre-treatment with pheophytin a at both the transcriptional and translational levels. Pheophytin a inhibited NOS2 promoter activity, but not its mRNA stability, through extracellular signal-regulated kinase (ERK1/2). This suppression was reversed by ERK1/2 inhibitor (U0126). Pheophytin a reduced signal transducers and activators of transcription 1 (STAT-1) activation, without an obvious influence on activator protein-1 (AP-1) and nuclear factor κB (NF-κB). These results suggest that pheophytin a functions by down-regulating the transcriptional levels of inflammatory mediators and blocking the ERK and STAT-1 pathways.


Asunto(s)
Dinoprostona/metabolismo , Inflamación/metabolismo , Interleucina-1beta/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Feofitinas/farmacología , Animales , Línea Celular , Ciclooxigenasa 2/metabolismo , Lipopolisacáridos/farmacología , Ratones , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Feofitinas/toxicidad , Factor de Transcripción STAT1/metabolismo , Transducción de Señal/efectos de los fármacos , Factor de Transcripción AP-1/metabolismo
17.
Molecules ; 19(4): 4234-45, 2014 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-24705566

RESUMEN

Sixteen compounds were extracted and purified from the leaves of Liriodendron tulipifera. These compounds include aporphines, oxoaporphine, coumarin, sesquiterpene lactone, benzenoids, cyclitol and steroids. (+)-Norstephalagine (2) (an aporphine) and scopoletin (8) (a coumarin) were isolated from Liriodendron tulipifera leaves from the first time. The identified compounds were screened for their antiradical scavenging, metal chelating and ferric reducing power activities. The results have showed that these compounds have antioxidative activity. The study has also examined the chemopreventive property of the isolated compounds against human melanoma cells A375. The results shown that (-)-anonaine (1), (-)-liridinine (3), (+)-lirinidine (6), lysicamine (7) and epitulipinolide diepoxide (9) significantly inhibited the proliferation of melanoma cells. These results revealed that these compounds have antioxidative activity and chemopreventive activity in skin melanoma cells.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Antioxidantes/farmacología , Liriodendron/química , Hojas de la Planta/química , Alcaloides/aislamiento & purificación , Alcaloides/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Antioxidantes/aislamiento & purificación , Aporfinas/aislamiento & purificación , Aporfinas/farmacología , Línea Celular Tumoral , Dioxoles/aislamiento & purificación , Dioxoles/farmacología , Humanos , Extractos Vegetales/química , Escopoletina/aislamiento & purificación , Escopoletina/farmacología
18.
Molecules ; 19(11): 17829-38, 2014 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-25372397

RESUMEN

Fifteen compounds were extracted and purified from the leaves of Nelumbo nucifera Gaertn. cv. Rosa-plena. These compounds include liriodenine (1), lysicamine (2), (-)-anonaine (3), (-)-asimilobine (4), (-)-caaverine (5), (-)-N-methylasimilobine (6), (-)-nuciferine (7), (-)-nornuciferine (8), (-)-roemerine (9), 7-hydroxydehydronuciferine (10) cepharadione B (11), ß-sitostenone (12), stigmasta-4,22-dien-3-one (13) and two chlorophylls: pheophytin-a (14) and aristophyll-C (15). The anti-oxidation activity of the compounds was examined by antiradical scavenging, metal chelating and ferric reducing power assays. The results have shown that these compounds have antioxidative activity. The study has also examined the antiproliferation activity of the isolated compounds against human melanoma, prostate and gastric cancer cells. The results shown that 7-hydroxydehydronuciferine (10) significantly inhibited the proliferation of melanoma, prostate and gastric cancer cells. Together, these findings suggest that leaves of Nelumbo nucifera Gaertn. cv. Rosa-plena are a good resource for obtaining the biologically active substances with antioxidant properties.


Asunto(s)
Alcaloides/farmacología , Antineoplásicos/farmacología , Antioxidantes/farmacología , Aporfinas/farmacología , Nelumbo/química , Hojas de la Planta/química , Rosa/química , Alcaloides/química , Antineoplásicos/química , Antioxidantes/química , Aporfinas/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Extractos Vegetales/química , Extractos Vegetales/farmacología
19.
Phytomedicine ; 132: 155855, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-39043083

RESUMEN

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a frequently occurring type of head and neck cancer with a high mortality and morbidity rate. Rhopaloic acid A (RA), a terpenoid derived from sponges, has demonstrated a promising anti-tumor activity, but its effectiveness for treating OSCC remains unknown. PURPOSE: The aim of this study was to investigate whether RA inhibits the growth of OSCC. METHODS: Cell viability was evaluated using CCK-8 assays in OSCC cells (Ca9-22, HSC-3 and SAS) and in normal cells (HGF-1) treated with RA. DAPI staining, AO staining, JC-1 staining and immunofluorescence were used to determine apoptosis, mitochondrial membrane potential and autophagy in RA-treated OSCC cells. Protein expression levels were determined by western blotting. Furthermore, the anti-tumor effect of RA was confirmed in vivo using a zebrafish oral cancer xenotransplantation model. RESULTS: OSCC cells had a significantly reduced viability after RA treatment, but normal cells were not affected. Treatment with RA caused chromatin condensation in OSCC cells, which increased their expression of autophagy- and apoptosis-related proteins. Furthermore, RA caused mitochondrial damage and increased autophagosome formation. Mitophagy was also induced by RA through the JNK/BNIP3/Nix/LC3B pathway. The JNK inhibitor SP600125 prevented both RA-mediated cell death and mitophagy of OSCC cells. A zebrafish xenograft model demonstrated that RA inhibits OSCC growth. CONCLUSION: In conclusion, RA showed a potent anticancer activity in in vitro and in in vivo oral cancer models by promoting mitochondrial damage-induced apoptosis and mitophagy, which suggests that RA may be useful as a novel and effective treatment for OSCC.

20.
Pharmaceuticals (Basel) ; 17(2)2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38399445

RESUMEN

The anti-oral cancer effects of santamarine (SAMA), a Michelia compressa var. compressa-derived natural product, remain unclear. This study investigates the anticancer effects and acting mechanism of SAMA against oral cancer (OC-2 and HSC-3) in parallel with normal (Smulow-Glickman; S-G) cells. SAMA selectively inhibits oral cancer cell viability more than normal cells, reverted by the oxidative stress remover N-acetylcysteine (NAC). The evidence of oxidative stress generation, such as the induction of reactive oxygen species (ROS) and mitochondrial superoxide and the depletion of mitochondrial membrane potential and glutathione, further supports this ROS-dependent selective antiproliferation. SAMA arrests oral cancer cells at the G2/M phase. SAMA triggers apoptosis (annexin V) in oral cancer cells and activates caspases 3, 8, and 9. SAMA enhances two types of DNA damage in oral cancer cells, such as γH2AX and 8-hydroxy-2-deoxyguanosine. Moreover, all of these anticancer mechanisms of SAMA are more highly expressed in oral cancer cells than in normal cells in concentration and time course experiments. These above changes are attenuated by NAC, suggesting that SAMA exerts mechanisms of selective antiproliferation that depend on oxidative stress while maintaining minimal cytotoxicity to normal cells.

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