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1.
Biochem Biophys Res Commun ; 530(1): 336-341, 2020 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-32828308

RESUMO

Radiotherapy is a crucial approach for treating tumors. However, radiation-induced aseptic inflammation is a common complication. Radiation pneumonitis is the acute manifestation of radiation-induced lung disease, and interleukin 6 (IL-6) is a major proinflammatory cytokine involved in radiation-induced lung injury. Here we found that silencing Zinc finger and BTB domain-containing protein 7B (Zbtb7b) resulted in higher radiation-induced IL-6 production in THP1 cells and BEAS-2B lung bronchial epithelial cells. Mechanistically, Zbtb7b recruited RNA demethylase ALKBH5 to IL6 mRNA. Subsequentially, it demethylated N6-methyladenosine (m6A) modification of IL6 mRNA and inhibited its nuclear export. Thus, Zbtb2b epigenetically suppresses irradiation-induced IL-6 production in the lungs via inhibiting the m6A modification and nucleocytoplasmic transport of IL6 mRNA, serving as a new potential predictive marker and therapeutic target in radiation pneumonitis treatment.


Assuntos
Adenosina/análogos & derivados , Proteínas de Ligação a DNA/genética , Inflamação/genética , Interleucina-6/genética , RNA Mensageiro/genética , Fatores de Transcrição/genética , Adenosina/genética , Linhagem Celular , Epigênese Genética , Células Epiteliais/metabolismo , Células Epiteliais/efeitos da radiação , Inativação Gênica , Células HEK293 , Humanos
2.
Mol Med Rep ; 17(5): 6828-6834, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29512751

RESUMO

Haishengsu (HSS) is an active natural extract isolated from Tegillarca granosa, which has previously been demonstrated to inhibit the proliferation of several types of cancer cells in vitro. Our previous study indicated that HSS may induce apoptosis to suppress growth of human hepatocellular carcinoma BEL­7402 cells by activating Fas pathway. The present study demonstrated that HSS treatment induces the in vitro apoptosis of BEL­7402 cells via the mitochondrial­mediated apoptotic pathway detected by DNA fragmentation assay, caspase activity assay and transmission electron microscopy assay, and inhibits tumor xenograft growth in vivo. Alterations in apoptotic regulatory proteins were detected, including decreased expression of B­cell lymphoma2 (Bcl­2), upregulation of Bcl­2­associated X protein and mitochondrial cytochrome c release, and downstream activation of apoptotic signaling. Furthermore, apoptotic induction was caspase­dependent, as indicated by cleavage of the caspase substrate, poly (ADP­ribose) polymerase. Oral administration of 62.5­250 mg/kg HSS markedly educed the growth of hepatocellular carcinoma tumor xenografts in nude mice. In addition, immunohistochemical staining for caspase­3 protein and transmission electron microscopy further indicated the induction of apoptosis in these tumor tissues. Taken together, the present study demonstrated that HSS may effectively induce apoptosis to suppress the growth of BEL­7402 cells in vitro and in vivo, and therefore may hold promise for further development as a novel cancer therapy.


Assuntos
Apoptose/efeitos dos fármacos , Bivalves/química , Carcinoma Hepatocelular , Misturas Complexas/farmacologia , Neoplasias Hepáticas , Mitocôndrias/metabolismo , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Caspase 3/metabolismo , Linhagem Celular Tumoral , Misturas Complexas/química , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Mitocôndrias/patologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína X Associada a bcl-2/metabolismo
3.
Acta Pharmacol Sin ; 37(2): 264-75, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26707141

RESUMO

AIM: Physcion, an anthraquinone derivative, exhibits hepatoprotective, anti-inflammatory, anti-microbial and anti-cancer activities. In this study we examined whether and how physcion inhibited metastatic potential of human colorectal cancer cells in vitro. METHODS: Human colorectal cancer cell line SW620 was tested. Cell migration and invasion were assessed using a wound healing and Transwell assay, respectively. The expression levels of transcription factor SOX2 in the cells were modulated with shRNA targeting SOX2 and SOX2 overexpressing plasmid. The expression of target molecules involved in epithelial-mesenchymal transition (EMT) process and the signaling pathways was determined with Western blots or qRT-PCR. ROS levels were measured using DCF-DA. RESULTS: Physcion (2.5, 5 mol/L) did not affect the cell viability, but dose-dependently inhibited the cell adhesion, migration and invasion. Physcion also inhibited the EMT process in the cells, as evidenced by the increased epithelial marker E-cadherin expression, and by decreased expression of mesenchymal markers N-cadherin, vimentin, fibronectin and α-SMA, as well as transcriptional repressors Snail, Slug and Twist. Physcion suppressed the expression of SOX2, whereas overexpression of SOX2 abrogated the inhibition of physcion on metastatic behaviors. Physcion markedly increased ROS production and phosphorylation of AMPK and GSK3ß in the cells, whereas the AMPK inhibitor compound C or the ROS inhibitor NAC abolished the inhibition of physcion on metastatic behaviors. CONCLUSION: Physcion inhibits the metastatic potential of human colorectal cancer cells in vitro via activating ROS/AMPK/GSK3ß signaling pathways and suppressing SOX2.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Regulação para Baixo/efeitos dos fármacos , Emodina/análogos & derivados , Metástase Neoplásica/prevenção & controle , Fatores de Transcrição SOXB1/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Linhagem Celular Tumoral , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Emodina/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Espécies Reativas de Oxigênio/metabolismo , Reto/efeitos dos fármacos , Reto/metabolismo , Reto/patologia , Transdução de Sinais/efeitos dos fármacos
4.
Biomed Pharmacother ; 69: 345-8, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25661380

RESUMO

l-Carnitine (LC) has protective effects on high glucose-induced oxidative stress in the retinal ganglion cells (RGCs). The aim of this study was to investigate the role of NF-E2-related factor 2 (Nrf2), Kelch like-ECH-associated protein 1 (Keap1), haemoxygenase-1 (HO-1) and γ-glutamyl cysteine synthetase (γ-GCS) in the protective effect of LC on RGCs. RGCs were first processed with high concentrations of glucose. LC treatment at three concentrations (50µM, 100µM and 200µM) was applied to high glucose stimulated RGCs. The expression of Nrf2, Keap1, haemoxygenase-1 (HO-1) and γ-glutamyl cysteine synthetase (γ-GCS) was quantified by Western blot in the treatment and control (high glucose stimulation) groups. In the three LC groups (50µM, 100µM and 200µM), Nrf-2 (0.71±0.04, 0.89±0.05, 1.24±0.05 vs 0.56±0.03, p<0.05), HO-1 (0.58±0.04, 0.76±0.06, 0.89±0.07 vs 0.25±0.03, p<0.01), and γ-GCS protein expression (0.66±0.03, 0.79±0.05, 0.84±0.08 vs 0.84±0.08, p<0.01) was higher than in the control group. The levels of Keap1 protein were in the LC groups were lower than in the control group (0.50±0.03, 0.45±0.02, 0.53±0.03 vs 0.86±0.05, p<0.01). In conclusion, in high glucose stimulated RGCs, LC treatment was associated with an increased level of Nrf2, HO-1and γ-GCS. LC treatment was also associated with a reduced expression of Keap1 protein. These results suggest that the protective effect of LC treatment on RGCs may be related to Nrf2-Keap1 pathway.


Assuntos
Carnitina/farmacologia , Glucose/toxicidade , Fator 2 Relacionado a NF-E2/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Células Ganglionares da Retina/metabolismo , Células Ganglionares da Retina/patologia , Animais , Forma Celular/efeitos dos fármacos , Glutamato-Cisteína Ligase/metabolismo , Heme Oxigenase-1 , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch , Ratos Wistar , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/enzimologia
5.
J Biomed Sci ; 19: 32, 2012 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-22435679

RESUMO

BACKGROUND: Excessive oxidative stress and lipid peroxidation have been demonstrated to play important roles in the production of liver damage. L-carnitine is a natural substance and acts as a carrier for fatty acids across the inner mitochondrial membrane for subsequent beta-oxidation. It is also an antioxidant that reduces metabolic stress in the cells. Recent years L-carnitine has been proposed for treatment of various kinds of disease, including liver injury. This study was conducted to evaluate the protective effect of L-carnitine against hydrogen peroxide (H2O2)-induced cytotoxicity in a normal human hepatocyte cell line, HL7702. METHODS: We analyzed cytotoxicity using MTT assay and lactate dehydrogenase (LDH) release. Antioxidant activity and lipid peroxidation were estimated by reactive oxygen species (ROS) levels, activities and protein expressions of superoxide dismutase (SOD) and catalase (CAT), and malondialdehyde (MDA) formation. Expressions of peroxisome proliferator-activated receptor (PPAR)-alpha and its target genes were evaluated by RT-PCR or western blotting. The role of PPAR-alpha in L-carnitine-enhanced expression of SOD and CAT was also explored. Statistical analysis was performed by a one-way analysis of variance, and its significance was assessed by Dennett's post-hoc test. RESULTS: The results showed that L-carnitine protected HL7702 cells against cytotoxity induced by H2O2. This protection was related to the scavenging of ROS, the promotion of SOD and CAT activity and expression, and the prevention of lipid peroxidation in cultured HL7702 cells. The decreased expressions of PPAR-alpha, carnitine palmitoyl transferase 1 (CPT1) and acyl-CoA oxidase (ACOX) induced by H2O2 can be attenuated by L-carnitine. Besides, we also found that the promotion of SOD and CAT protein expression induced by L-carnitine was blocked by PPAR-alpha inhibitor MK886. CONCLUSIONS: Taken together, our findings suggest that L-carnitine could protect HL7702 cells against oxidative stress through the antioxidative effect and the regulation of PPAR-alpha also play an important part in the protective effect.


Assuntos
Carnitina/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , PPAR alfa/metabolismo , Acil-CoA Oxidase/genética , Acil-CoA Oxidase/metabolismo , Carnitina O-Palmitoiltransferase/genética , Carnitina O-Palmitoiltransferase/metabolismo , Catalase/genética , Catalase/metabolismo , Linhagem Celular , Hepatócitos/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/farmacologia , Indóis/farmacologia , Malondialdeído/metabolismo , PPAR alfa/antagonistas & inibidores , PPAR alfa/genética , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1
6.
Zhonghua Xin Xue Guan Bing Za Zhi ; 40(10): 854-7, 2012 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-23302674

RESUMO

OBJECTIVE: To summary the efficacy and safety of aerosolized iloprost in patients with pulmonary hypertensive crisis. METHODS: On the basis of conventional therapy, aerosolized iloprost (10 µg per time for 10 - 15 min in 2 hours interval, 8 times per day) was administered to four patients with idiopathic pulmonary arterial hypertension and pulmonary hypertensive crisis. Blood pressure, heart rate, systemic artery oxygen saturation, systolic pulmonary arterial pressure (sPAP) measured by echocardiography and the adverse events were analyzed. RESULTS: After aerosolized iloprost therapy, sPAP was significantly decreased and systemic artery oxygen saturation was improved. Adverse events (nausea, vomiting, diarrhea, dry cough) were observed in two patients, and the iloprost use was stopped in one patient due to severe vomiting and diarrhea. CONCLUSION: Aerosolized iloprost could significantly reduce the sPAP and improve the systemic artery oxygen saturation in patients with pulmonary hypertension crisis.


Assuntos
Hipertensão Pulmonar/tratamento farmacológico , Iloprosta/administração & dosagem , Iloprosta/uso terapêutico , Administração por Inalação , Adulto , Pressão Sanguínea , Criança , Hipertensão Pulmonar Primária Familiar , Feminino , Humanos , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
7.
Cell Physiol Biochem ; 28(5): 865-72, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22178939

RESUMO

AIMS: Purple sweet potato (PSP) pigments were proved to protect murine thymocytes from (60)Co γ-ray-induced mitochondria-mediated apoptosis in our previous study. In this study, we further investigated the effect of PSP pigments on apoptosis related ROS, p53 and Bcl-2 family. METHODS: Cell viability was analyzed by MTT. Apoptosis was certified by DNA ladder detection. Reactive oxygen species (ROS) were detected using 2',7',- dichlorofluorescein diacetate (DCFH-DA) probe. P53, Bcl-2 and Bax proteins were analyzed by western blot. The activities of caspase-3 and caspase-9 were determined by fluorogenic substrates detection. RESULTS: PSP pigments treatment prior to 4Gy (60)Co γ-ray irradiation increased the cell viability and decrease the apoptosis. In the presence of PSP pigments, ROS was scavenged and followed by a p53-depression. A shift in Bcl-2/Bax ratio towards anti-apoptosis was observed as a result of p53-depression. The activities of caspase-9 and caspase-3 were reduced by PSP pigments pretreatment. CONCLUSIONS: PSP pigments have a cytoprotective activity against γ radiation. The protective effect of PSP pigments may be involving ROS scavenging, p53 depression and Bcl-2/Bax modulation in a caspase-dependent mitochondrial way.


Assuntos
Apoptose/efeitos dos fármacos , Pigmentos Biológicos/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Timócitos/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/metabolismo , Animais , Apoptose/efeitos da radiação , Caspase 3/metabolismo , Caspase 9/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Radioisótopos de Cobalto/química , Fragmentação do DNA , Inibidores Enzimáticos/farmacologia , Raios gama , Ipomoea batatas/química , Camundongos , Pigmentos Biológicos/metabolismo , Timócitos/efeitos da radiação
8.
Tohoku J Exp Med ; 224(3): 209-13, 2011 07.
Artigo em Inglês | MEDLINE | ID: mdl-21701126

RESUMO

L-carnitine has been used as a supplement to treat cardiovascular or liver disease. However, there has been little information about the effect of L-carnitine on anti-oxidation capability in healthy human subjects. This study was designed to investigate the correlation between plasma L-carnitine concentration and antioxidant activity. Liquid L-carnitine (2.0 g) was administered orally as a single dose in 12 healthy subjects. Plasma concentration of L-carnitine was detected by HPLC. The baseline concentration of L-carnitine was 39.14 ± 5.65 µmol/L. After single oral administration, the maximum plasma concentration (C(max)) and area under the curve (AUC(0-∞)) were 84.7 ± 25.2 µmol/L and 2,676.4 ± 708.3 µmol/L·h, respectively. The half-life and the time required to reach the C(max) was 60.3 ± 15.0 min and 3.4 ± 0.46 h, respectively. There was a gradual increase in plasma concentrations of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase and total antioxidative capacity (T-AOC) in the first 3.5 h following L-carnitine administration. The plasma concentrations of SOD, GSH-Px, catalase and T-AOC returned to baseline levels within 24 h. A positive correlation was found between L-carnitine concentration and the antioxidant index of SOD (r = 0.992, P < 0.01), GSH-Px (r = 0.932, P < 0.01), catalase (r = 0.972, P < 0.01) or T-AOC (r = 0.934, P < 0.01). In conclusion, L-carnitine increases activities of antioxidant enzymes and the total antioxidant capacity in healthy subjects. It may be useful as a supplementary therapy for chronic illnesses involving excessive oxidative stress.


Assuntos
Antioxidantes/metabolismo , Carnitina/administração & dosagem , Carnitina/farmacologia , Saúde , Administração Oral , Carnitina/sangue , Carnitina/farmacocinética , Catalase/metabolismo , Relação Dose-Resposta a Droga , Glutationa Peroxidase/metabolismo , Humanos , Superóxido Dismutase/metabolismo , Fatores de Tempo
9.
Int J Radiat Biol ; 86(12): 1061-9, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20698744

RESUMO

PURPOSE: Purple sweet potato (PSP) pigments have been widely accepted as antioxidants but their radioprotective effect still remains unclear. In this study we investigated the effect of PSP pigments on 6°Co γ-ray-induced mitochondria-mediated apoptosis in murine thymocytes. MATERIALS AND METHODS: The murine thymocytes were pretreated by PSP pigments before exposure to 4 Gy 6°Co γ-rays. Flow cytometry analysis was used to measure apoptotic cells and mitochondrial membrane potential. Reactive oxygen species (ROS) were detected using 2',7',-dichlorofluorescein diacetate (DCFH-DA) probe and the activity of antioxidant enzymes was tested by biochemical assay after irradiation. Cytochrome c, caspase-3 and poly ADP-ribose polymerase (PARP) were measured by Western blotting. RESULTS: After treatment with PSP pigments and exposure to 4 Gy radiation the apoptosis of thymocytes was reduced and the mitochondrial transmembrane potential was maintained compared to control cells. In the presence of PSP pigments, ROS were reduced and the activities of glutathione peroxidase (GSH-px) and superoxide dismutase (SOD) were protected and in some cases increased. All the pro-apoptotic proteins (cytochrome oxidase, caspase 3 and PARP) decreased in PSP pigments pretreated thymocytes compared to irradiated cells in the absence of PSP pigments. CONCLUSIONS: Pre-treatment with PSP pigments significantly inhibited 6°Co γ-ray-induced mitochondria-mediated apoptosis. This radioprotective effect might be related to ROS scavenging, the enhancement of the activity of antioxidant enzymes, the maintenance of mitochondrial transmembrane potential, and the sequential inhibition of cytochrome c release and downstream caspase and PARP cleavage.


Assuntos
Pigmentos Biológicos/farmacologia , Protetores contra Radiação/farmacologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/efeitos da radiação , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Caspase 3/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Células Cultivadas , Radioisótopos de Cobalto/toxicidade , Citocromos c/metabolismo , Raios gama/efeitos adversos , Glutationa Peroxidase/metabolismo , Ipomoea batatas , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos da radiação , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos da radiação , Poli(ADP-Ribose) Polimerases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Linfócitos T/metabolismo , Linfócitos T/patologia
10.
Pharm Biol ; 48(5): 529-33, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20645795

RESUMO

This study was designed to investigate the effect and molecular mechanisms of Haishengsu (HSS), a protein extract from a shellfish Tegillarca granosaL., on a drug resistant leukemia cell line. Cultured K562/Adriamycin (ADM) cells were treated with HSS at 10, 20 and 40 microg/mL, respectively. The apoptosis and expression of p-glycoprotein was evaluated by flow cytometry. Expressions of caspase-3 and Bcl-2 were also evaluated. There was a significant dose-dependent increase in the apoptosis in the HSS treated K562/ADM cells (P < 0.05 and 0.01, respectively). The p-glycoprotein expression in the 40 microg/mL HSS group (14.8%) was lower than in the control (16.9%, P < 0.05) and the 10 microg/mL HSS group (7.3%, P < 0.05), but it was similar to the HSS 20 microg/mL group (10.7%, P > 0.05). The expressions of apoptosis-stimulating protein caspase-3 protein were increased, whereas the expressions of apoptosis-suppressing Bcl-2 were decreased in the HSS groups, as compared with the levels in the control group (P < 0.05). We conclude that HSS induces apoptosis of the Adriamycin-resistant K562/ADM cells. The enhanced expressions in caspase-3 and the reduced expressions in Bcl-2 protein may have contributed to the apoptosis-stimulating effect of HSS. The inhibition of p-glycoprotein suggests that HSS may diminish the resistance to Adriamycin and potentially enhance the therapeutic effects.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Albuminas/farmacologia , Apoptose/efeitos dos fármacos , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/biossíntese , Albuminas/isolamento & purificação , Animais , Apoptose/fisiologia , Resistencia a Medicamentos Antineoplásicos/fisiologia , Medicamentos de Ervas Chinesas/isolamento & purificação , Humanos , Células K562 , Projetos Piloto , Frutos do Mar
11.
J Altern Complement Med ; 15(10): 1127-30, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19821717

RESUMO

OBJECTIVE: The purpose of this study was to investigate the effect of Haishengsu, an extract from Tegillarca L. granosa, on the effects and side-effects of immunotherapy in patients with advanced renal cell cancer. METHODS: Fifty-five (55) patients with renal cell cancer were randomly divided into a Haishengsu group (n = 27, 2.4 mg, intravenously for 15 days) and a control group (n = 28). All patients were also treated with interleukin-2, interferon-alpha, and fluorouracil. RESULTS: In the Haishengsu group, the prevalence of gastrointestinal reactions to the immunotherapy was lower than in the control group (18.5% versus 64.3%, p < 0.01). In comparison with the control group, more patients from the Haishengsu group had increased food intake (74.1% versus 14.3%, p < 0.01), weight gain (77.8% versus 10.7%, p < 0.01) or an increase in Karnofsky Performance Status score (55.6% versus 17.9%, p < 0.01). The remission rate of cancer in the Haishengsu group was higher than in the control group (51.9% and 21.4%, p < 0.01). CONCLUSIONS: Addition of Haishengsu to the conventional immunotherapy is associated with an increased remission rate in patients with advanced renal cell cancer. Haishengsu was also associated with a reduced rate of gastrointestinal side-effects from the immunotherapeutic agents, and an improvement in the physical functionality of the patients.


Assuntos
Albuminas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Trato Gastrointestinal/efeitos dos fármacos , Neoplasias Renais/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Albuminas/farmacologia , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Arcidae , Quimioterapia Adjuvante , Medicamentos de Ervas Chinesas/farmacologia , Ingestão de Energia/efeitos dos fármacos , Feminino , Fluoruracila/administração & dosagem , Humanos , Interferon-alfa/administração & dosagem , Interleucina-2/administração & dosagem , Avaliação de Estado de Karnofsky , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Indução de Remissão , Aumento de Peso/efeitos dos fármacos
12.
Clin Invest Med ; 32(5): E368-75, 2009 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-19796578

RESUMO

PURPOSE: To determine the cellular and molecular mechanism of cytotoxicity induced by Haishengsu (HSS), nature extract from Tegillarca granosa, toward human ovarian cancer cell lines SKOV-3 and OVCAR-3. METHODS: The cytotoxic effects of HSS on two ovarian cancer cell lines were tested by XTT assay. Cell apoptosis and cell cycle arrest induced by HSS were demonstrated by DNA ladder assay and flow cytometric analysis, respectively. RT-PCR or flow cytometric analysis was used to investigate the expression of bcl-2, caspase-3, p53, beta-catenin, E-cadherin, CD24, and CD44. RESULTS: Continuous exposure to HSS for 48 h produced cytotoxic effects on both cell lines in a concentration dependent manner, which was accompanied by apoptosis and cell cycle arrest. Apoptosis associated gene bcl-2 and caspase-3, tumor metastasis associated gene ?-catenin, but not E-cadherin, and CD24, but not CD44, were involved in the effect of growth inhibition induced by HSS. Although p53 mediated apoptosis induced by HSS in OVCAR-3 cells, it was not required in SKOV-3 cells. CONCLUSION: HSS has a potential cytotoxic effect on human ovarian cancer cells, which was mediated by multiple signal molecules including bcl-2, caspase-3, beta-catenin, and CD24. These findings will provide a theoretical basis for HSS's potential clinical application as a novel marine anti-cancer agent.


Assuntos
Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Arcidae/química , Animais , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Antígeno CD24/metabolismo , Caspase 3/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Receptores de Hialuronatos/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteína Supressora de Tumor p53/metabolismo , beta Catenina/metabolismo
13.
Immunopharmacol Immunotoxicol ; 31(4): 669-74, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19874239

RESUMO

This study was designed to investigate the effect of a seashell protein Haishengsu (HSS) on the immuno logical function in mice with Ehrlich ascites tumor. Ehrlich ascites tumor-bearing mice were divided into three HSS groups (25, 50 and 100 mg/kg, i.v., respectively), cyclophosphamide (10 mg i.p.) and control group. The immunological function was assessed by measuring the phagocytizing capacity of the peritoneal macrophages and neutrophils, as well as the number of spleen hemolytic plaque-forming cells. The percentage of blood T-lymphocytes was also evaluated. The number and the percentage of phagocytizing macrophages and neutrophils in the 50 and 100 mg/kg HSS groups were higher than in the control and the cyclophosphamide groups (P < 0.01). The hemolytic plaque-forming cells in the three HSS groups (10.8 +/- 1.2, 16.9 +/- 3.9 and 25.3 +/- 2.9, respectively), was greater than in the control (7.3 +/- 1.4), or the cyclophosphamide group (0.33 +/- 0.4) (all P < 0.01). In all HSS groups, the percentage of blood T3, T4 and T8 was higher than in the cyclophosphamide and the control group (all P < 0.01). We conclude that HSS has significant immune-modulating effect in mice with Ehrlich ascites tumor.


Assuntos
Albuminas/uso terapêutico , Carcinoma de Ehrlich/tratamento farmacológico , Carcinoma de Ehrlich/imunologia , Medicamentos de Ervas Chinesas/uso terapêutico , Albuminas/farmacologia , Animais , Galinhas , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fagocitose/efeitos dos fármacos , Fagocitose/imunologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia
14.
J Nat Med ; 63(4): 459-62, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19536610

RESUMO

The aim of the study was to investigate the in vivo effect of the seashell protein Haishengsu (HSS) on Ehrlich ascites tumor. Mice were inoculated with Ehrlich ascites tumor cells and randomly divided into three HSS groups and a control group. The survival times in the three HSS-treated groups was longer than in the control (P < 0.01) and the increased life span in the high-dose HSS group was greater than in the lower-dose groups (P < 0.05). In comparison with control group, the mice receiving pretreatment of HSS had longer survival times and greater life spans following inoculation of the ascites tumor (P < 0.05). HSS therefore prolongs survival times and increases the life spans of mice bearing Ehrlich ascites tumor. Pretreatment with HSS also diminishes the detrimental effect of Ehrlich ascites tumor on the prognosis of these animals.


Assuntos
Albuminas/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma de Ehrlich/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Animais , Carcinoma de Ehrlich/prevenção & controle , Camundongos , Análise de Sobrevida
15.
Clin Invest Med ; 32(2): E117-23, 2009 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-19331800

RESUMO

PURPOSE: To evaluate the effect of Haishengsu (HSS) on transplanted K562 and drug-resistant K562/ADM tumors. METHODS: Mice were inoculated subcutaneously with K562 and K562/ADM cells, respectively. Tumour-bearing animals were divided into HSS, adriamycin, combination therapy (adriamycin plus HSS) and placebo groups. The anti-tumour effect was assessed by tumour growth curve and tumour inhibitory rate (IR). RESULTS: In animals inoculated with K562 cells, the inhibitory rates of high (1800mg/kg) and medium (900mg/kg ) dose HSS groups were 100% and 96.4%, respectively, which was higher than that in the adriamycin (88.9%) or the combination therapy groups (85.8%, P < 0.05). The inhibitory rate in the low-dose HSS group (53.4%) was lower than in all other groups (P < 0.01). In mice inoculated with K562/ADM cells, the inhibitory rates in the high, medium and low dose HSS groups were 100%, 95.9%, and 44.1%, respectively. In the adriamycin group, the inhibitory rate was 23.07%, which was lower than in the HSS group (P < 0.01). Pathological examination of tumour tissues from HSS-treated animals showed extensive necrosis and bleeding. CONCLUSIONS: Haishengsu inhibits the growth of transplanted K562 tumours in mice. It is also effective in suppressing the growth of drug-resistant K562/ADM tumors in this animal model.


Assuntos
Albuminas/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Leucemia Experimental/tratamento farmacológico , Albuminas/farmacologia , Animais , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/uso terapêutico , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Células K562 , Leucemia Experimental/patologia , Camundongos , Camundongos Nus , Transplante de Neoplasias
16.
Clin Invest Med ; 32(1): E13-9, 2009 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-19178874

RESUMO

PURPOSE: To investigate the pharmacokinetics of L-carnitine (LC) and its analogues, acetyl-L-carnitine (ALC) and propionyl-L-carnitine (PLC) in healthy volunteers after single L-carnitine administration. METHODS: Liquid L-carnitine (2.0 g) was administered orally as a single dose in 12 healthy subjects. Plasma and urine concentrations of L-carnitine, ALC and PLC were detected by HPLC. RESULTS: The maximum plasma concentration (Cmax) and area under the curve (AUC 0-infinity) of L-carnitine was 84.7+/-25.2 micromol x L(-1) x h and 2676.4+/-708.3 micromol x L(-1) x h, respectively. The elimination half-life of L-carnitine and the time required to reach the Cmax (Tmax) was 60.3+/-15.0 and 3.4+/-0.46 h, respectively. The Cmax of ALC (12.9+/-5.5 micromol x L(-1)) and PLC (5.08+/-3.08 micromol x L(-1)) was lower than L-carnitine (P < 0.01), so as the AUC 0-infinity (166.2+/-77.4 and 155.6+/-264.2 micromol x L(-1) x h, respectively, P < 0.01). The half-life of ALC (35.9+/-28.9h) and PLC (25.7+/-30.3 h) was also shorter than L-carnitine (P < 0.01). The 24h accumulated urinary excretion of L-carnitine, ALC and PLC were 613.5+/-161.7, 368.3+/-134.8 and 61.3+/-37.8 micromol, respectively. CONCLUSION: L-carnitine has a greater maximum plasma concentration than ALC and PLC. L-carnitine also has a longer half-life than ALC and PLC. These data may have important implications in the designing of dosing regimens for L-carnitine or its analogues, such as ALC or PLC.


Assuntos
Acetilcarnitina/farmacocinética , Carnitina/análogos & derivados , Carnitina/farmacocinética , Acetilcarnitina/sangue , Administração Oral , Adulto , Área Sob a Curva , Carnitina/administração & dosagem , Carnitina/sangue , Cromatografia Líquida de Alta Pressão , Feminino , Meia-Vida , Humanos , Masculino , Valores de Referência
17.
Biomed Pharmacother ; 63(8): 566-70, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19095404

RESUMO

This study was designed to investigate the effects of cyclosporine A (CsA) on a multidrug resistance cultured cell line, and its effect on complete remission in patients with acute myeloid leukemia (AML). A multidrug resistant K562/ADM cell line and drug-sensitive K562 cell line was used. The intracellular concentration of daunorubicin and the accumulation of Rhodamine 123 (Rh123) in the K562/ADM and K562 cells were evaluated. Clinical effects of CsA were also studied in 65 patients with AML. In the K562/ADM cells, the 50% of inhibition concentration (IC50) of daunorubicin only group was 23.0+/-5.2 micromol/L, which was greater than in other groups co-administered with CsA (1.2+/-4.8 micromol/L), verapamil (1.5+/-5.4 micromol/L) or CsA+verapamil (1.4+/-4.3 micromol/L) (all P<0.01). The relative fluorescence intensity of Rh123 in the K562/ADM cells treated with CsA and daunorubicin was increased from 48.9% to 69.8% (P<0.05). CsA also improved the complete remission rate in the AML patients (72.7% vs 21.9%, P<0.01). We conclude that CsA can significantly diminish the multidrug resistance in K562/ADM cells. It also enhances the complete remission rates in patients with AML. CsA may be used as an integral part of the chemotherapy for AML.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Leucemia Mieloide Aguda/tratamento farmacológico , Subfamília B de Transportador de Cassetes de Ligação de ATP , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Adulto , Antibióticos Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/metabolismo , Transporte Biológico , Sobrevivência Celular/efeitos dos fármacos , Ciclosporina/administração & dosagem , Citarabina/administração & dosagem , Daunorrubicina/farmacologia , Relação Dose-Resposta a Droga , Feminino , Corantes Fluorescentes/metabolismo , Humanos , Idarubicina/administração & dosagem , Concentração Inibidora 50 , Células K562 , Leucemia Mieloide Aguda/metabolismo , Masculino , Rodamina 123/metabolismo , Fatores de Tempo , Resultado do Tratamento , Verapamil/administração & dosagem
18.
Complement Ther Med ; 17(1): 51-5, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19114229

RESUMO

OBJECTIVE: To investigate the effect of Haishengsu, an extract from Tegillarca granosa, on non-small cell lung cancer as an adjunct to conventional chemotherapy. DESIGNS/SETTINGS: Randomized, double-blind, placebo-controlled trial was conducted in 83 patients. The Haishengsu (n=42, 2.4mg Haishengsu in 250ml normal saline, iv, for 15 days) and the placebo group (n=41, 250ml normal saline, iv) were also treated with two cycles (28 days for each cycle) of conventional chemotherapy consisting mitomycin, vindesine and cisplatin. RESULTS: The curative effect of conventional chemotherapy was observed in 62% of Haishengsu group patients and in 39% in of the placebo group patients (P=0.04, RR 1.59, 95% CI: 1.01-2.49). Improvement in Karnofsky performance status scores was seen in 66.7% of Haishengsu group patients and in 17.1% of the placebo group patients (P<0.01, RR 3.63, 95%CI: 1.77-7.41). The ratio of patients with no or only mild gastrointestinal reaction in the Haishengsu and the placebo group was 83.3% and 39.0%, respectively (P<0.01, RR 2.13, 95% CI: 1.42-3.20). CONCLUSIONS: This study suggests that Haishengsu may be an effective adjunct therapy to the conventional chemotherapy for non-small cell lung cancer. The short-term therapeutic effect of chemotherapy may be improved and the chemotherapy-induced nausea or vomiting may be reduced by concurrent Haishengsu administration.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Moluscos , Animais , Peso Corporal , Quimioterapia Adjuvante , Progressão da Doença , Ingestão de Alimentos , Trato Gastrointestinal/fisiopatologia , Humanos , Avaliação de Estado de Karnofsky , Masculino , Medicina Tradicional Chinesa , Pessoa de Meia-Idade , Náusea/tratamento farmacológico , Projetos Piloto , Vômito/tratamento farmacológico
19.
Clin Invest Med ; 31(4): E218-21, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18682046

RESUMO

OBJECTIVES: To investigate the effect of a seashell protein Haishengsu (HSS), an extract from a shellfish Tegillarca granosa, on cell growth and the expression of apoptosis genes in leukemia K562 cells. METHODS: Cultured K562 cells were treated with HSS at various concentrations (10-40 mg/L). The cell cycle, cell growth and the expression of apoptosis suppressor gene bcl-2 and apoptosis promoting gene bax were evaluated. RESULTS: HSS, 20mg/L, inhibited cell cycle in the G0/G1 and S phases. HSS, 20mg/L, also inhibited the growth of K562 cells over time. Expression of bcl-2 gene in the HSS 20mg/L (58.8%+/-4.7%) and HSS 40 mg/L group (26.6%+/-2.1%) were lower than in the control group (91.0+/-8.7%, P < 0.01). Expression of bax gene in the HSS 20mg/L (77.7+/-3.6%) and 40 mg/L group (90.6+/-3.7%) were higher than in the control group (10.9+/-6.6%, P < 0.01). CONCLUSION: HSS suppresses leukemia K562 cell growth by inhibiting the G0/G1 and S phases of the cell cycle. It also induces apoptosis in these leukemia cells by reducing the expression of apoptosis suppressor gene bcl-2, and increasing the expression of apoptosis promoting gene bax. Further studies are required to investigate the clinical efficacy of HSS in leukemia.


Assuntos
Albuminas/farmacologia , Apoptose/efeitos dos fármacos , Arcidae/química , Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Animais , Apoptose/fisiologia , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/fisiologia , Regulação Neoplásica da Expressão Gênica/fisiologia , Genes bcl-2/genética , Genes bcl-2/fisiologia , Humanos , Imuno-Histoquímica , Células K562 , Células Tumorais Cultivadas , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
20.
Free Radic Res ; 42(1): 12-9, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18324519

RESUMO

Polypeptide from Chlamys farreri (PCF), a novel marine active material isolated from gonochoric Chinese scallop C. farreri, has potential antioxidant activity and protective effect against ultraviolet (UV) irradiation. The aim was to investigate whether PCF protects HaCaT cells from apoptosis induced by UVA and explore related molecular mechanisms. The results showed that PCF significantly prevented UVA-induced apoptosis of HaCaT cells. PCF not only strongly reduced the intracellular reactive oxygen species (ROS) production, but also diminished expression of acid sphingomyelinase (ASMase) and phosphorylated JNK in HaCaT cells radiated by UVA in a dose-dependent manner. Pre-treatment with ROS scavenger NAC, ASMase inhibitor desipramine or JNK inhibitor SP600125 was found to effectively prohibit UVA-induced apoptosis and desipramine markedly blocked phosphorylation of JNK. So it is concluded that PCF obviously protects HaCaT cells from apoptosis induced by UVA and protective effects may attribute to decreasing intracellular ROS level and blocking ASMase/JNK apoptotic signalling pathway.


Assuntos
Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Queratinócitos/efeitos dos fármacos , Pectinidae , Peptídeos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Esfingomielina Fosfodiesterase/metabolismo , Raios Ultravioleta , Acetilcisteína/farmacologia , Animais , Antracenos/farmacologia , Antioxidantes/isolamento & purificação , Linhagem Celular , Desipramina/farmacologia , Relação Dose-Resposta a Droga , Ativação Enzimática , Sequestradores de Radicais Livres/farmacologia , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Queratinócitos/enzimologia , Queratinócitos/metabolismo , Queratinócitos/patologia , Queratinócitos/efeitos da radiação , Pectinidae/química , Peptídeos/isolamento & purificação , Fosforilação , Inibidores de Proteínas Quinases/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação , Esfingomielina Fosfodiesterase/antagonistas & inibidores
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