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1.
PLoS One ; 16(8): e0254929, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34383763

RESUMO

In searching for novel targeted therapeutic agents for lung cancer treatment, norcycloartocarpin from Artocarpus gomezianus was reported in this study to promisingly interacted with Akt and exerted the apoptosis induction and epithelial-to-mesenchymal transition suppression. Selective cytotoxic profile of norcycloartocarpin was evidenced with approximately 2-fold higher IC50 in normal dermal papilla cells (DPCs) compared with human lung cancer A549, H460, H23, and H292 cells. We found that norcycloartocarpin suppressed anchorage-independent growth, cell migration, invasion, filopodia formation, and decreased EMT in a dose-dependent manner at 24 h, which were correlated with reduced protein levels of N-cadherin, Vimentin, Slug, p-FAK, p-Akt, as well as Cdc42. In addition, norcycloartocarpin activated apoptosis caspase cascade associating with restoration of p53, down-regulated Bcl-2 and augmented Bax in A549 and H460 cells. Interestingly, norcycloartocarpin showed potential inhibitory role on protein kinase B (Akt) the up-stream dominant molecule controlling EMT and apoptosis. Computational molecular docking analysis further confirmed that norcycloartocarpin has the best binding affinity of -12.52 kcal/mol with Akt protein at its critical active site. As Akt has recently recognized as an attractive molecular target for therapeutic approaches, these findings support its use as a plant-derived anticancer agent in cancer therapy.

2.
In Vivo ; 35(5): 2589-2597, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34410946

RESUMO

BACKGROUND/AIM: Dermal papilla cells (DPCs) regulate hair follicle development. We aimed to investigate the effect of scoparone from Dendrobium densiflorum on DPCs in the induction of stem cell properties and pluripotency-related proteins. MATERIALS AND METHODS: DPC viability was evaluated by the MTT assay. Apoptosis or necrosis of DPCs was determined by Hoecsht33342/PI nuclear staining analysis. Expression of OCT4, NANOG and SOX2 genes was determined using Real-Time Polymerase Chain Reaction (PCR). Immunocytochemistry and western blot analysis were performed to determine pluripotency related proteins. RESULTS: Scoparone increased the expression of pluripotency related transcription factors SOX2 and NANOG, while it had minimal effects on OCT4 levels. Scoparone exerted its stemness-enhancing activity through the up-regulation of Akt-dependent inhibition of GSK3ß, resulting in increased cellular levels of ß-catenin. CONCLUSION: Our results show a potential novel activity and mechanism of action of scoparone on human DPCs that could facilitate the development of hair enrichment approaches.


Assuntos
Cumarínicos , Células-Tronco , Apoptose , Folículo Piloso , Humanos , Proteína Homeobox Nanog/genética , Proteína Homeobox Nanog/metabolismo , Fatores de Transcrição SOXB1/genética , Células-Tronco/metabolismo , Regulação para Cima
3.
J Asian Nat Prod Res ; : 1-6, 2021 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-34304660

RESUMO

From the whole plant of Dendrobium senile, a new phenanthrene namely 2,5,7-trihydroxy-4-methoxyphenanthrene (1) was isolated, together with seven known compounds including moscatin (2), 2,5-dihydroxy-4,9-dimethoxyphenanthrene (3), moscatilin (4), aloifol I (5), 4,4',8,8'-tetramethoxy[1,1'-biphenanthrene]-2,2',7,7'-tetrol (6), 2,2',7,7'-tetrahydroxy-4,4'-dimethoxy-1,1'-biphenanthrene (7) and bleformin G (8). The structure of the new compound was elucidated by analysis of its spectroscopic data. Moscatin (2) and 2,5-dihydroxy-4,9-dimethoxyphenanthrene (3) showed appreciable pancreatic lipase inhibitory effects when compared with the positive control orlistat.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34287120

RESUMO

Three novel actinomycete strains, designated as DR6-1T, DR6-2 and DR6-4, isolated from the roots of Dendrobium heterocarpum Lindl in Thailand were studied using a polyphasic taxonomic approach. The strains grew at 20-37 °C, at pH 5-10 and with 5 % (w/v) NaCl. They contained meso-diaminopimelic acid in the cell-wall peptidoglycan and MK-9(H4) was a major menaquinone. Arabinose and galactose were the major sugars in the cell wall. The predominant cellular fatty acids were iso-C16 : 0 and iso-C15 : 0. The detected polar lipids were diphosphatidylglycerol, hydroxyphosphatidylethanolamine, phosphatidylethanolamine, phosphatidylinositol and phosphatidylglycerol. Strains DR6-1T, DR6-2 and DR6-4 shared 99.9-100 % 16S rRNA gene sequence similarity and were closely related to Amycolatopsis echigonensis JCM 21831T (98.7-98.8%). The approximate genome size of strain DR6-1T was 9.6 Mb with a G+C content of 69.6 mol%. The ANIb and dDDH values between genomic sequences of strain DR6-1T and Amycolatopsis echigonensis JCM21831T, Amycolatopsis rubida JCM 10871T and Amycolatopsis nivea KCTC 39515T were 90.55, 92.25, 92.60%, and 47.20, 52.10 and 52.50%, respectively. Based on the phenotypic, chemotaxonomic and genotypic characteristics, it has been concluded that strains DR6-1T, DR6-2 and DR6-4 represent a novel species of the genus Amycolatopsis for which the name Amycolatopsis dendrobii sp. nov. is proposed. The type strain is DR6-1T (=JCM 33742T=KCTC 49546T=TISTR 2840T).


Assuntos
Amycolatopsis/classificação , Dendrobium/microbiologia , Filogenia , Amycolatopsis/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Graxos/química , Hantavirus , Peptidoglicano/química , Fosfolipídeos/química , Raízes de Plantas/microbiologia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
5.
Int J Mol Sci ; 22(13)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34202163

RESUMO

Lusianthridin is a phenanthrene derivative isolated from Dendrobium venustum. Some phenanthrene compounds have antiplatelet aggregation activities via undefined pathways. This study aims to determine the inhibitory effects and potential mechanisms of lusianthridin on platelet aggregation. The results indicated that lusianthridin inhibited arachidonic acid, collagen, and adenosine diphosphate (ADP)-stimulated platelet aggregation (IC50 of 0.02 ± 0.001 mM, 0.14 ± 0.018 mM, and 0.22 ± 0.046 mM, respectively). Lusianthridin also increased the delaying time of arachidonic acid-stimulated and the lag time of collagen-stimulated and showed a more selective effect on the secondary wave of ADP-stimulated aggregations. Molecular docking studies revealed that lusianthridin bound to the entrance site of the cyclooxygenase-1 (COX-1) enzyme and probably the active region of the cyclooxygenase-2 (COX-2) enzyme. In addition, lusianthridin showed inhibitory effects on both COX-1 and COX-2 enzymatic activities (IC50 value of 10.81 ± 1.12 µM and 0.17 ± 1.62 µM, respectively). Furthermore, lusianthridin significantly inhibited ADP-induced suppression of cAMP formation in platelets at 0.4 mM concentration (p < 0.05). These findings suggested that possible mechanisms of lusianthridin on the antiplatelet effects might act via arachidonic acid-thromboxane and adenylate cyclase pathways.


Assuntos
Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Fenantrenos/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Difosfato de Adenosina/metabolismo , AMP Cíclico , Ciclo-Oxigenase 1/química , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/química , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase/química , Inibidores de Ciclo-Oxigenase/farmacologia , Humanos , Modelos Moleculares , Conformação Molecular , Fenantrenos/química , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/farmacologia , Relação Estrutura-Atividade
6.
Anticancer Res ; 41(8): 3843-3849, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34281844

RESUMO

BACKGROUND/AIM: Integrin-targeting compounds have shown clinically significant benefits in many patients. Here, we examined the activity of millettocalyxin B, extracted from the stem bark of Millettia erythrocalyx, in lung cancer cells. MATERIALS AND METHODS: The viability of human lung cancer cells was investigated by the 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyl tetrazoliumbromide (MTT) assay. Migration and invasion assays were performed. Phalloidin-rhodamine staining was used to determine the formation of filopodia. Western blot analysis and immunofluorescence staining were used to identify the signaling proteins involved in migration regulation. RESULTS: Non-toxic concentrations (0-25 µM) of millettocalyxin B reduced migration and invasion of lung cancer A549 cells. Filopodia were significantly reduced in millettocalyxin B-treated cells. The migration regulatory proteins including integrin α5, active FAK, active Akt, and Cdc42 were significantly decreased in Millettocalyxin B-treated cells. CONCLUSION: Our findings revealed a novel anti-migration and anti-invasion effects and the underlying mechanism of millettocalyxin B, which may be exploited for cancer treatment.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Flavonoides/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Células A549 , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Quinase 1 de Adesão Focal/metabolismo , Humanos , Integrina alfa5/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pseudópodes/efeitos dos fármacos , Proteína cdc42 de Ligação ao GTP/metabolismo
7.
Anticancer Res ; 41(6): 2913-2923, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34083282

RESUMO

BACKGROUND/AIM: Epithelial to mesenchymal transition (EMT), and focal adhesion kinase (FAK) facilitate lung cancer cell motility and survival. We, therefore, investigated the antimigratory effect of 3,4-dihydroxy-5,4'-dimethoxybibenzyl (DS-1) on human lung cancer cells. MATERIALS AND METHODS: Cell viability and proliferation were examined by the 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide assay. Filopodia formation, migration, and anchorage-independent growth assays were performed to assess metastatic behaviors while EMT-related proteins, integrins, and FAK-RhoA pathway were evaluated by western blot analysis. RESULTS: We found that DS-1 significantly inhibited the proliferation of lung cancer cells compared to the control. The aggressive behavior of cancer cells, including migration and invasion, was significantly reduced by DS-1. Anchorage-independent growth analysis provided evidence that DS-1 suppressed the growth and survival of cancer cells in detached conditions as indicated by the significant reduction in size and number of colonies. With regard to the mechanisms involved, we found that DS-1-suppressed EMT, as indicated by the reduction of EMT markers, namely N-cadherin, SNAIL and SLUG, and increased levels of the epithelial marker, E-cadherin. In addition, DS-1 was shown to reduce the level of integrin ß1 protein and FAK activation. CONCLUSION: DS-1 suppressed lung cancer metastasis via suppressing EMT, integrin ß1 expression and FAK-related signaling.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Proteína-Tirosina Quinases de Adesão Focal/antagonistas & inibidores , Integrina beta1/efeitos dos fármacos , Neoplasias Pulmonares/patologia , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Humanos , Integrina beta1/metabolismo
8.
Sci Rep ; 11(1): 6618, 2021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33758209

RESUMO

Cancer metastasis is a major cause of the high mortality rate in lung cancer patients. The cytoskeletal rearrangement and degradation of extracellular matrix are required to facilitate cell migration and invasion and the suppression of these behaviors is an intriguing approach to minimize cancer metastasis. Even though Erianthridin (ETD), a phenolic compound isolated from the Thai orchid Dendrobium formosum exhibits various biological activities, the molecular mechanism of ETD for anti-cancer activity is unclear. In this study, we found that noncytotoxic concentrations of ETD (≤ 50 µM) were able to significantly inhibit cell migration and invasion via disruption of actin stress fibers and lamellipodia formation. The expression of matrix metalloproteinase-2 (MMP-2) and MMP-9 was markedly downregulated in a dose-dependent manner after ETD treatment. Mechanistic studies revealed that protein kinase B (Akt) and its downstream effectors mammalian target of rapamycin (mTOR) and p70 S6 kinase (p70S6K) were strongly attenuated. An in silico study further demonstrated that ETD binds to the protein kinase domain of Akt with both hydrogen bonding and van der Waals interactions. In addition, an in vivo tail vein injection metastasis study demonstrated a significant effect of ETD on the suppression of lung cancer cell metastasis. This study provides preclinical information regarding ETD, which exhibits promising antimetastatic activity against non-small-cell lung cancer through Akt/mTOR/p70S6K-induced actin reorganization and MMPs expression.

9.
Phytomedicine ; 85: 153534, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33773191

RESUMO

BACKGROUND: Lung cancer is a leading fatal malignancy due to the high incidence of treatment failure. Dysfunction of the tumor suppressor p53 contributes to cancer initiation, progression, and therapeutic resistance. Targeting MDM2, a negative regulator of p53, has recently attracted interest in cancer drug research as it may restore tumor suppressive function. PURPOSE: The present study aimed to investigate the effect of 3,4-dihydroxy-5,4'-dimethoxybibenzyl (DS-1) on targeting MDM2 and restoring p53 function in lung cancer cells. METHODS: The efficacy of DS-1 alone or in combination with cisplatin in lung cancer cells was determined by MTT, nuclear staining, and annexin V/PI assay. The expression of apoptosis-related proteins was determined by western blot analysis. To evaluate the role of DS-1 on the stabilization and degradation of p53, cycloheximide chasing assay and immunoprecipitation were conducted, and the active form of p53 was investigated by immunofluorescent staining assay. To confirm and demonstrate the site interaction between DS-1 and the MDM2 protein, in silico computational analysis was performed. RESULTS: DS-1 exhibited a cytotoxic effect and sensitized lung cancer cells to cisplatin-induced apoptosis. DS-1 caused a significant increase in the cellular level of p53 protein, while the active form of p53 (phosphorylation at Ser15) was unaltered. DS-1 treatment in combination with cisplatin could enhance activated p-p53 (Ser15) and p53 downstream signaling (Bax, Bcl-2, and Akt), leading to a higher level of apoptosis. Immunoprecipitation analysis revealed that DS-1 decreased the p53-ubiquitin complex, a prerequisite step in p53 proteasomal degradation. Molecular docking simulation further evidenced that DS-1 interacts with MDM2 within the p53-binding domain by carbon-hydrogen bond interaction at Lys27, π-alkyl interactions at Ile37 and Leu30, and van der Waals interactions at Ile75, Val51, Val69, Phe67, Met38, Tyr43, Gly34, and Phe31. Treatment by DS-1 and cisplatin in patient-derivated primary lung cancer cells showed consistent effects by increasing cisplatin sensitivity. CONCLUSIONS: Our findings provide evidence that DS-1 is an MDM2 inhibitor and its underlying mechanism involves MDM2 binding and p53 induction, which may benefit the development of this compound for lung cancer treatment.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Bibenzilas/farmacologia , Neoplasias Pulmonares/patologia , Proteínas Proto-Oncogênicas c-mdm2/antagonistas & inibidores , Proteína Supressora de Tumor p53/metabolismo , Adulto , Idoso , Linhagem Celular Tumoral , Cisplatino/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Simulação de Acoplamento Molecular , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Transdução de Sinais/efeitos dos fármacos
11.
Plants (Basel) ; 10(2)2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33671404

RESUMO

A phytochemical investigation on the whole plants of Aerides multiflora revealed the presence of three new biphenanthrene derivatives named aerimultins A-C (1-3) and a new natural phenylpropanoid ester dihydrosinapyl dihydroferulate (4), together with six known compounds (5-10). The structures of the new compounds were elucidated by analysis of their spectroscopic data. All of the isolates were evaluated for their α-glucosidase inhibitory activity. Aerimultin C (3) showed the most potent activity. The other compounds, except for compound 4, also exhibited stronger activity than the positive control acarbose. Compound 3 showed non-competitive inhibition of the enzyme as determined from a Lineweaver-Burk plot. This study is the first phytochemical and biological investigation of A. multiflora.

12.
Molecules ; 26(3)2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33530617

RESUMO

Cancer metastasis is the major cause of about 90% of cancer deaths. As epithelial-to-mesenchymal transition (EMT) is known for potentiating metastasis, this study aimed to elucidate the effect of ovalitenone on the suppression of EMT and metastasis-related behaviors, including cell movement and growth under detached conditions, and cancer stem cells (CSCs), of lung cancer cells. METHODS: Cell viability and cell proliferation were determined by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazo-liumbromide (MTT) and colony formation assays. Cell migration and invasion were analyzed using a wound-healing assay and Boyden chamber assay, respectively. Anchorage-independent cell growth was determined. Cell protrusions (filopodia) were detected by phalloidin-rhodamine staining. Cancer stem cell phenotypes were assessed by spheroid formation. The proteins involved in cell migration and EMT were evaluated by Western blot analysis and immunofluorescence staining. RESULTS: Ovalitenone was used at concentrations of 0-200 µM. While it caused no cytotoxic effects on lung cancer H460 and A549 cells, ovalitenone significantly suppressed anchorage-independent growth, CSC-like phenotypes, colony formation, and the ability of the cancer to migrate and invade cells. The anti-migration activity was confirmed by the reduction of filopodia in the cells treated with ovalitenone. Interestingly, we found that ovalitenone could significantly decrease the levels of N-cadherin, snail, and slug, while it increased E-cadherin, indicating EMT suppression. Additionally, the regulatory signaling of focal adhesion kinase (FAK), ATP-dependent tyrosine kinase (AKT), the mammalian target of rapamycin (mTOR), and cell division cycle 42 (Cdc42) was suppressed by ovalitenone. CONCLUSIONS: The results suggest that ovalitenone suppresses EMT via suppression of the AKT/mTOR signaling pathway. In addition, ovalitenone exhibited potential for the suppression of CSC phenotypes. These data reveal the anti-metastasis potential of the compound and support the development of ovalitenone treatment for lung cancer therapy.


Assuntos
Neoplasias Pulmonares/metabolismo , Millettia/química , Compostos Fitoquímicos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Células A549 , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Células-Tronco Neoplásicas/efeitos dos fármacos , Compostos Fitoquímicos/isolamento & purificação , Proteínas Proto-Oncogênicas c-akt/metabolismo
13.
Molecules ; 26(2)2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33466863

RESUMO

Four new phenanthrene derivatives, gastrobellinols A-D (1-4), were isolated from the methanolic extract of Gastrochilus bellinus (Rchb.f.) Kuntze, along with eleven known phenolic compounds including agrostophyllin (5), agrostophyllidin (6), coniferyl aldehyde (7), 4-hydroxybenzaldehyde (8), agrostophyllone (9), gigantol (10), 4-(methoxylmethyl)phenol (11), syringaldehyde (12), 1-(4'-hydroxybenzyl)-imbricartin (13), 6-methoxycoelonin (14), and imbricatin (15). Their structures were determined by spectroscopic methods. Each isolate was evaluated for α-glucosidase inhibitory activity. Compounds 1, 2, 3, 7, 9, 13, and 15 showed higher activity than the drug acarbose. Gastrobellinol C (3) exhibited the strongest α-glucosidase inhibition with an IC50 value of 45.92 µM. A kinetic study of 3 showed competitive inhibition on the α-glucosidase enzyme. This is the first report on the phytochemical constituents and α-glucosidase inhibitory activity of G. bellinus.


Assuntos
Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Orchidaceae/química , Fenantrenos/química , Extratos Vegetais/farmacologia , alfa-Glucosidases/química
14.
Bioprocess Biosyst Eng ; 44(4): 653-660, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33170382

RESUMO

Large amounts of Morus alba L. (MA) roots are needed as the source of active stilbenes in the industrial production of traditional medicines and cosmeceuticals. A recent investigation demonstrated resveratrol and its derivatives to be promising anti-COVID-19 agents. However, conventional cultivation of MA does not meet the demand for its stilbenes, and root quality usually varies between crops. This study established the in vitro non-GMO root culture of MA and optimized the root density, precursor feeding, and elicitors for stilbene productivity. A root culture with optimal inoculum density (3 g/flask of 30 mL medium) accumulated mulberroside A, oxyresveratrol, and resveratrol at 18.7 ± 1.00 mg/g, 136 ± 5.05 µg/g, and 41.6 ± 5.84 µg/g dry weight (DW), respectively. The feeding of L-tyrosine shortened the time required to reach the stilbene productive stage. Root cultures co-treated with 200 µM methyl jasmonate and 2 mg/mL yeast extract accumulated the highest contents of mulberroside A (30.3 ± 2.68 mg/g DW), oxyresveratrol (68.6 ± 3.53 µg/g DW), and resveratrol (10.2 ± 0.53 µg/g DW). In summary, root culture is a promising and sustainable source of stilbenes for the development of health products and agents for further investigation as potential anti-COVID-19 agents.


Assuntos
Morus , Células Vegetais/metabolismo , Raízes de Plantas , Estilbenos/metabolismo , COVID-19/tratamento farmacológico , Humanos , Morus/citologia , Morus/metabolismo , Raízes de Plantas/citologia , Raízes de Plantas/metabolismo , SARS-CoV-2 , Estilbenos/uso terapêutico
15.
Planta Med ; 87(4): 283-293, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33212515

RESUMO

Due to the high mortality of lung cancer, natural derivative compounds have been promoted as versatile sources for anticancer drug discovery. Erianthridin, a phenanthrene compound isolated from Dendrobium formosum, exhibits intriguing apoptosis-inducing effects in non-small cell lung cancer cells. Apoptotic nuclei staining assays showed that apoptotic cells with DNA fragmentation and apoptotic bodies were apparent, and an increase in annexin V-FITC-positive cells were found in cells treated with erianthridin. The apoptosis protein markers for cleaved caspase-3 and cleaved poly-ADP-ribose polymerase were significantly upregulated in response to erianthridin. A mechanistic investigation revealed that erianthridin was able to attenuate extracellular signal-regulated kinase activity and thereby mediate apoptosis through the modulation of Bcl-2 family protein levels. U0126, an extracellular signal-regulated kinase inhibitor, augmented the apoptosis-inducing effect of erianthridin; in contrast, overexpression of exogenous extracellular signal-regulated kinase substantially abrogated erianthridin activity. Furthermore, an in vitro 3D tumorigenesis assay showed that erianthridin was able to potentially suppress lung cancer cell proliferation. This study is the first to report a promising cytotoxic effect of erianthridin, which provides preclinical evidence for further research and development of this compound.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Fenantrenos , Apoptose , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Linhagem Celular Tumoral , MAP Quinases Reguladas por Sinal Extracelular , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Fenantrenos/farmacologia
16.
Molecules ; 25(21)2020 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-33113779

RESUMO

Two new compounds, dihydrodengibsinin (1) and dendrogibsol (2), were isolated from the whole plant of Dendrobium gibsonii, together with seven known compounds (3-9). The structures of the new compounds were elucidated by their spectroscopic data. All these isolates were evaluated for their α-glucosidase inhibitory activities. Dendrogibsol (2) and lusianthridin (7) showed strong α-glucosidase inhibitory activity when compared with acarbose. An enzyme kinetic study revealed that dendrogibsol (2) is a noncompetitive inhibitor of α-glucosidase.


Assuntos
Dendrobium/química , Fluorenos/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Extratos Vegetais/isolamento & purificação , alfa-Glucosidases/metabolismo , Fluorenos/metabolismo , Glucanos/química , Inibidores de Glicosídeo Hidrolases/metabolismo , Estrutura Molecular , Fenantrenos/isolamento & purificação , Fenantrenos/metabolismo , Extratos Vegetais/metabolismo , Solventes/química
17.
Molecules ; 25(21)2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33113908

RESUMO

The health benefits of the Aquilaria crassna Pierre ex Lecomte leaf extract (AE) make it very useful as an ingredient in food and pharmaceutical products. Iriflophenone 3,5-C-ß-d-diglucoside (1), iriflophenone 3-C-ß-d-glucoside (2) and mangiferin (3) are bioactive compounds of AE. We assessed the stability of AE by investigating the thermal degradation kinetics and shelf-life (t90%) of compounds 1, 2 and 3 using Arrhenius plot models and studied their pH-rate profiles. The results demonstrate that 1 and 2 were degraded, following a first-order kinetic reaction. The degradation of 3 followed first-order reaction kinetics when present in a solution and second-order reaction kinetics in the dried powder form of the extract. According to the first-order kinetic model, the predicted shelf-life (t90%) of the extract at 25 °C in dried form for compound 1 was 989 days with activation energy 129.86 kJ·mol-1, and for 2 it was 248 days with activation energy 110.57 kJ·mol-1, while in the extract solution, the predicted shelf-life of compounds 1-3 was 189, 13 and 75 days with activation energies 86.83, 51.49 and 65.28 kJ·mol-1, respectively. In addition, the pH-rate profiles of 1-3 indicated that they were stable in neutral to acidic environments.


Assuntos
Glucosídeos/química , Extratos Vegetais/química , Folhas de Planta/química , Lectinas de Plantas/química , Temperatura , Thymelaeaceae/química , Xantonas/química , Concentração de Íons de Hidrogênio , Cinética
18.
PLoS One ; 15(9): e0238509, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32870935

RESUMO

Dendrobium bibenzyls and phenanthrenes such as chrysotoxine, cypripedin, gigantol and moscatilin have been reported to show promising inhibitory effects on lung cancer growth and metastasis in ex vivo human cell line models, suggesting their potential for clinical application in patients with lung cancer. However, it remains to be determined whether these therapeutic effects can be also seen in primary human cells and/or in vivo. In this study, we comparatively investigated the immune modulatory effects of bibenzyls and phenanthrenes, including a novel Dendrobium bibenzyl derivative, in primary human monocytes. All compounds were isolated and purified from a Thai orchid Dendrobium lindleyi Steud, a new source of therapeutic compounds with promising potential of tissue culture production. We detected increased frequencies of TNF- and IL-6-expressing monocytes after treatment with gigantol and cypripedin, whereas chrysotoxine and moscatilin did not alter the expression of these cytokines in monocytes. Interestingly, the new 4,5-dihydroxy-3,3',4'-trimethoxybibenzyl derivative showed dose-dependent immune modulatory effects in lipopolysaccharide (LPS)-treated CD14lo and CD14hi monocytes. Together, our findings show immune modulatory effects of the new bibenzyl derivative from Dendrobium lindleyi on different monocyte sub-populations. However, therapeutic consequences of these different monocyte populations on human diseases including cancer remain to be investigated.


Assuntos
Bibenzilas/farmacologia , Dendrobium , Fatores Imunológicos/farmacologia , Monócitos/efeitos dos fármacos , Fenantrenos/farmacologia , Extratos Vegetais/farmacologia , Compostos de Benzil/química , Compostos de Benzil/farmacologia , Bibenzilas/química , Células Cultivadas , Dendrobium/química , Guaiacol/análogos & derivados , Guaiacol/química , Guaiacol/farmacologia , Humanos , Fatores Imunológicos/química , Monócitos/imunologia , Naftoquinonas/química , Naftoquinonas/farmacologia , Fenantrenos/química , Extratos Vegetais/química
19.
Anticancer Res ; 40(9): 4989-4999, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878787

RESUMO

BACKGROUND/AIM: Epithelial to mesenchymal transition (EMT) is a cellular process that facilitates cancer metastasis. Therefore, therapeutic approaches that target EMT have garnered increasing attention. The present study aimed to examine the in vitro effects of ephemeranthol A on cell death, migration, and EMT of lung cancer cells. MATERIALS AND METHODS: Ephemeranthol A was isolated from Dendrobium infundibulum. Non-small cell lung cancer cells H460 were treated with ephemeranthol A and apoptosis was evaluated by Hoechst 33342 staining. Anoikis resistance was determined by soft agar assay. Wound healing assay was performed to test the migration. The regulatory proteins of apoptosis and cell motility were determined by western blot. RESULTS: Treatment with ephemeranthol A resulted in a concentration-dependent cell apoptosis. At non-toxic concentrations, the compound could inhibit anchorage-independent growth of the cancer cells, as indicated by the decreased colony size and number. Ephemeranthol A also exhibited an inhibitory effect on migration. We further found that ephemeranthol A exerts its antimetastatic effects via inhibition of EMT, as indicated by the markedly decrease of N-cadherin, vimentin, and Slug. Furthermore, the compound suppressed the activation of focal adhesion kinase (FAK) and protein kinase B (Akt) proteins, which are key regulators of cell migration. As for the anticancer activity, ephemeranthol A induced apoptosis by decreasing Bcl-2 followed by the activation of caspase 3 and caspase 9. CONCLUSION: The pro-apoptotic and anti-migratory effects of ephemeranthol A on human lung cancer cells support its use for the development of novel anticancer therapies.


Assuntos
Antineoplásicos/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Quinase 1 de Adesão Focal/metabolismo , Neoplasias Pulmonares/patologia , Fenantrenos/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dendrobium/química , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Estrutura Molecular , Fenantrenos/química , Fenantrenos/uso terapêutico
20.
Molecules ; 25(15)2020 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-32748832

RESUMO

The phytochemical investigation of Huberantha jenkinsii resulted in the isolation of two new and five known compounds. The new compounds were characterized as undescribed 8-oxoprotoberberine alkaloids and named huberanthines A and B, whereas the known compounds were identified as allantoin, oxylopinine, N-trans-feruloyl tyramine, N-trans-p-coumaroyl tyramine, and mangiferin. The structure determination was accomplished by spectroscopic methods. To evaluate therapeutic potential in diabetes and Parkinson's disease, the isolates were subjected to assays for their α-glucosidase inhibitory activity, cellular glucose uptake stimulatory activity, and protective activity against neurotoxicity induced by 6-hydroxydopamine (6-OHDA). The results suggested that mangiferin was the most promising lead compound, demonstrating significant activity in all the test systems.


Assuntos
Annonaceae/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Animais , Biomarcadores , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Glucose/metabolismo , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Ratos , Relação Estrutura-Atividade
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