RESUMEN
Equol is a metabolite of daidzein and has a higher biological activity than daidzein. Equol, combined with estrogen receptors, can reduce the incidence of diseases such as cardiovascular disease, osteoporosis, and breast cancer; more effectively alleviate the symptoms of perimenopausal syndrome; and improve age-related decline of the uterus and ovaries. Research has shown that food composition can greatly affect the formation of equol in the intestinal tract. In the intestines, the content of nonstarch polysaccharides that can stimulate fermentation is high, thereby allowing intestinal bacteria to quickly and completely transform the daidzein into equol. This study used Sprague Dawley (SD) rats as a model, where menopause was established through direct intragastric administration of formistan. In the 6-week-long experiment, intragastric administration of RS while feeding bean pulp reduced the body weight of postmenopausal rats, reduced the efficiency of feed utilization of rats, and increased the weight of organs such as the uterus and ovaries. Routine blood indexes showed that no adverse reactions were produced by intragastric administration of RS. 16s rDNA sequencing further verified Lactobacillus and Clostridium XIVa, as the bacteria that converted daidzein into equol.
RESUMEN
Equol is a metabolite of daidzein and has a higher biological activity than daidzein. High levels of non-starch polysaccharides can stimulate fermentation in the intestine leading to rapid conversion of daidzein into equol that has great potential to reduce obesity in postmenopausal women. In the present study, female Sprague-Dawley rats were used to establish a menopausal model by oral administration of formestane and to compare the protective effect of resistant starch on lipid metabolism, with or without soybean feed. The resistant starch was found to effectively control body weight and adipose tissue quality, while increasing the high-density lipoprotein cholesterol (HDL-C) concentration and lowering the glycerol, triacylglycerols (TG), total cholesterol (TC), and low density lipoprotein cholesterol (LDL-C) concentrations with soybean feed. Equol inhibited the expression of SREBPC1 gene by inhibiting SHP in the liver via transcription factor FXR, thereby inhibiting the synthesis of triglyceride and fatty acid in the liver. PRACTICAL APPLICATIONS: Intake of a certain amount of resistant starch while eating the soy product can better regulate lipid metabolism in menopausal obese rats compared to consumption of resistant starch alone. Studies have shown that resistant starch converts daidzein to Equol by regulating the structure of the intestinal flora and acts as an estrogen in menopausal rats. This research will further expand the health applications of resistant starch and provide useful information for the food industry.
Asunto(s)
Equol , Sorghum , Animales , Femenino , Metabolismo de los Lípidos , Menopausia , Ratas , Ratas Sprague-Dawley , Almidón ResistenteRESUMEN
Liquiritin (LIQ), a major constituent of Glycyrrhiza Radix, exhibits various pharmacological activities. In this study, to explore the potential anti-cancer effects and its underlying molecular mechanisms of LIQ in hepatocellular carcinoma (HCC) cells. LIQ significantly decreased viability and induced apoptosis in HepG2 cells by decreasing mitochondrial membrane potential and regulating Bcl-2 family proteins, cytochrome c, cle-caspase-3, and cle-PARP. The cell cycle analysis and western blot analysis revealed that LIQ induced G2/M phase arrest through increased expression of p21 and decreased levels of p27, cyclin B, and CDK1/2. The flow cytometry and western blot analysis also suggested that LIQ promoted the accumulation of ROS in HepG2 cells and up-regulated the phosphorylation expression levels of p38 kinase, c-Jun N-terminal kinase (JNK), and inhibitor of NF-κB (IκB-α); the phosphorylation levels of extracellular signal-regulated kinase (ERK), protein kinase B (AKT), signal transducer activator of transcription 3 (STAT3), and nuclear factor kappa B (NF-κB) were down-regulated. However, these effects were reversed by N-acetyl-L-cysteine (NAC), MAPK, and AKT inhibitors. The findings demonstrated that LIQ induced cell cycle arrest and apoptosis via the ROS-mediated MAPK/AKT/NF-κB signaling pathway in HepG2 cells, and the LIQ may serve as a potential therapeutic agent for the treatment of human HCC.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Proliferación Celular/efectos de los fármacos , Flavanonas/farmacología , Glucósidos/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , FN-kappa B/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Antineoplásicos Fitogénicos/uso terapéutico , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Proliferación Celular/fisiología , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Relación Dosis-Respuesta a Droga , Flavanonas/uso terapéutico , Glucósidos/uso terapéutico , Glycyrrhiza , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Sistema de Señalización de MAP Quinasas/fisiología , FN-kappa B/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Cytisine is a natural product isolated from plants and is a member of the quinolizidine alkaloid family. This study aims to investigate the effect of cytisine in human lung cancer. Cell viability was determined using the CCK-8 assay, and the results showed that cytisine inhibited the growth of lung cancer cell lines. The apoptotic effects were evaluated using flow cytometry, and the results showed that cytisine induced mitochondrial-dependent apoptosis through loss of the mitochondrial membrane potential; increased expression of BAD, cleaved caspase-3, and cleaved-PARP; and decreased expression levels of Bcl-2, pro-caspase-3, and pro-PARP. In addition, cytisine caused G2/M phase cell cycle arrest that was associated with inhibiting the AKT signalling pathway. During apoptosis, cytisine increased the phosphorylation levels of JNK, p38, and I-κB, and decreased the phosphorylation levels of ERK, STAT3, and NF-κB. Furthermore, cytisine treatment led to the generation of ROS, and the NAC attenuated cytisine-induced apoptosis. In vivo, cytisine administration significantly inhibited the lung cancer cell xenograft tumorigenesis. In conclusion, cytisine plays a critical role in suppressing the carcinogenesis of lung cancer cells through cell cycle arrest and induction of mitochondria-mediated apoptosis, suggesting that it may be a promising candidate for the treatment of human lung cancer.
Asunto(s)
Alcaloides/farmacología , Antineoplásicos/farmacología , Neoplasias Pulmonares/patología , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Azocinas/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Humanos , Puntos de Control de la Fase M del Ciclo Celular/efectos de los fármacos , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Quinolizinas/farmacología , Factor de Transcripción STAT3/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The 1,4-naphthoquinones and their derivatives have garnered great interest due to their antitumor pharmacological properties in various cancers; however, their clinical application is limited by side effects. In this study, to reduce side effects and improve therapeutic efficacy, a novel 1,4-naphthoquinone derivative-2-(4-methoxyphenylthio)-5,8-dimethoxy-1,4-naphthoquinone (MPTDMNQ) was synthesized. We investigated the effects and underlying mechanisms of MPTDMNQ on cell viability, apoptosis, and reactive oxygen species (ROS) generation in human gastric cancer cells. Our results showed that MPTDMNQ decreased cell viability in nine human gastric cancer cell lines. MPTDMNQ significantly induced apoptosis accompanied by the accumulation of ROS in GC cells. However, pre-treatment with the ROS scavenger N-acetyl-L-cysteine (NAC) attenuated the MPTDMNQ-induced apoptosis. Moreover, MPTDMNQ decreased the phosphorylation levels of extracellular signal-regulated kinase (ERK) and signal transducer and activator of transcription 3 (STAT3); and increased the phosphorylation levels of c-Jun N-terminal kinase (JNK) and p38 kinase. However, phosphorylation was inhibited by NAC and a mitogen-activated protein kinase (MAPK) inhibitor. These findings showed that MPTDMNQ induced AGS cell apoptosis via ROS-mediated MAPK and STAT3 signaling pathways. Thus, MPTDMNQ may be a promising candidate for treating gastric cancer.
Asunto(s)
Apoptosis/efectos de los fármacos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Naftoquinonas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Factor de Transcripción STAT3/metabolismo , Neoplasias Gástricas/tratamiento farmacológico , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Humanos , Transducción de Señal/efectos de los fármacos , Neoplasias Gástricas/metabolismoRESUMEN
Isoliquiritigenin (ISL), a natural flavonoid isolated from plant licorice, has various pharmacological properties, including anticancer, anti-inflammatory, and antiviral effects. However, the underlying mechanisms and signaling pathways of ISL in human hepatocellular carcinoma (HCC) cells remain unknown. In this study, we evaluated the effects of ISL on the apoptosis of human HCC cells with a focus on reactive oxygen species (ROS) production. Our results showed that ISL exhibited cytotoxic effects on two human liver cancer cells in a dose-dependent manner. ISL significantly induced mitochondrial-related apoptosis and cell cycle arrest at the G2/M phase, which was accompanied by ROS accumulation in HepG2 cells. However, pretreatment with an ROS scavenger, N-acetyl-l-cysteine (NAC), inhibited ISL-induced apoptosis. In addition, ISL increased the phosphorylation levels of c-Jun N-terminal kinase (JNK), p38 kinase and inhibitor of NF-κB (IκB), and decreased the phosphorylation levels of extracellular signal-regulated kinase (ERK), signal transducer and activator of transcription 3 (STAT3), nuclear factor-kappa B (NF-κB), these effects were blocked by NAC and mitogen-activated protein kinase (MAPK) inhibitors. Taken together, the findings of this study indicate that ISL induced HepG2 cell apoptosis via ROS-mediated MAPK, STAT3, and NF-κB signaling pathways. Therefore, ISL may be a potential treatment for human HCC, as well as other cancer types.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Chalconas/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Técnicas de Cultivo de Célula , Supervivencia Celular/efectos de los fármacos , Células Hep G2 , Humanos , FN-kappa B/metabolismo , Factor de Transcripción STAT3/metabolismoRESUMEN
The present study investigated the mechanisms of apoptosis induced by cryptotanshinone (CT) in human rheumatoid arthritis fibroblastlike synoviocytes (RAFLSs). Cell Counting kit8 assay was performed to determine the cytotoxic effects of CT in human RAFLSs, including primary RAFLS, HFLSRA and MH7A cells, and in HFLS cells derived from normal synovial tissue. Annexin VFITC/PI staining was used to detect the apoptotic effects of CT in HFLSRA and MH7A cells. Flow cytometry was performed to detect the apoptotic and reactive oxygen species (ROS) levels induced by CT in HFLSRA cells. Western blotting was used to assess the expression levels of proteins associated with apoptosis and with the mitogenactivated protein kinase (MAPK), protein kinase B (Akt), and signal transducer and activator of transcription3 (STAT3) signaling pathways. The results demonstrated that CT treatment significantly suppressed HFLSRA and MH7A cell growth, whereas no clear inhibitory effect was observed in normal HFLS cells. CT exposure downregulated the expression levels of Bcell lymphoma 2 (Bcl2), pAkt, pextracellular signalrelated kinase and pSTAT3, while it upregulated the expression levels of Bcl2associated death promoter (Bad), caspase3, poly (ADPribose) polymerase (PARP), pp38 and pcJun Nterminal kinase. Following ROS scavenging, the CTinduced apoptosis and altered expression levels of Bcl2, Bad, cleaved caspase3 and cleaved PARP were restored. Furthermore, the Akt, MAPK and STAT3 signaling pathways were regulated by intracellular ROS. These results suggest that ROSmediated Akt, MAPK and STAT3 signaling pathways serve important roles in the CTinduced apoptosis of RAFLSs.
Asunto(s)
Apoptosis/efectos de los fármacos , Artritis Reumatoide/metabolismo , Fenantrenos/farmacología , Especies Reactivas de Oxígeno/metabolismo , Sinoviocitos/efectos de los fármacos , Sinoviocitos/metabolismo , Biomarcadores , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Fibroblastos/metabolismo , Humanos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factor de Transcripción STAT3/metabolismoRESUMEN
Hit, Lead & Candidate Discovery It is reported that 1,4-naphthoquinones and their derivatives have potent antitumor activity in various cancers, although their clinical application is limited by observed side effects. To improve the therapeutic efficacy of naphthoquinones in the treatment of cancer and to reduce side effects, we synthesized a novel naphthoquinone derivative, 2-(naphthalene-2-thio)-5,8-dimethoxy-1,4-naphthoquinone (NTDMNQ). In this study, we explored the effects of NTDMNQ on apoptosis in gastric cancer cells with a focus on reactive oxygen species (ROS) production. Our results demonstrated that NTDMNQ exhibited the cytotoxic effects on gastric cancer cells in a dose-dependent manner. NTDMNQ significantly induced mitochondrial-related apoptosis in AGS cells and increased the accumulation of ROS. However, pre-treatment with N-acetyl-L-cysteine (NAC), an ROS scavenger, inhibited the NTDMNQ-induced apoptosis. In addition, NTDMNQ increased the phosphorylation of p38 kinase and c-Jun N-terminal kinase (JNK) and decreased the phosphorylation of extracellular signal-regulated kinase (ERK), protein kinase B (Akt), and Signal Transducer and Activator of Transcription 3 (STAT3); these effects were blocked by mitogen-activated protein kinase (MAPK) inhibitor and NAC. Taken together, the present findings indicate that NTDMNQ-induced gastric cancer cell apoptosis via ROS-mediated regulation of the MAPK, Akt, and STAT3 signaling pathways. Therefore, NTDMNQ may be a potential treatment for gastric cancer as well as other tumor types.