Myricetin inhibits proliferation of cisplatin-resistant cancer cells through a p53-dependent apoptotic pathway

Cisplatin is a commonly used drug for cancer treatment by crosslinking DNA, leading to apoptosis of cancer cells, resistance to cisplatin treatment often occurs, leading to relapse. Therefore, there is a need for the development of more effective treatment strategies that can overcome chemoresistance. Myricetin is a flavonoid from fruits and vegetables, showing anticancer activity in various cancer cells. In this study, we found myricetin exhibited greater cytotoxicity than cisplatin in two cisplatin-resistant ovarian cancer cell lines, OVCAR-3 and A2780/CP70, and it was less cytotoxic to the normal ovarian cell line IOSE-364. Myricetin selectively induced apoptosis in both cisplatin-resistant cancer cell lines, but did not induce apoptosis in the normal ovarian cell line. It induced both Bcl-2 family-dependent intrinsic and DR5 dependent extrinsic apoptosis in OVCAR-3 cells. P53, a multifunctional tumor suppressor, regulated apoptosis in OVCAR-3 cells through a Bcl-2 family protein-dependent pathway. Myricetin did not induce cell cycle arrest in either ovarian cancer cell line. Because of its potency and selectivity against cisplatin-resistant cancer cells, myricetin could potentially be used to overcome cancer chemoresistance against platinum-based therapy

Myricetin inhibits proliferation of cisplatin-resistant cancer cells through a p53-dependent apoptotic pathway

Cisplatin is a commonly used drug for cancer treatment by crosslinking DNA, leading to apoptosis of cancer cells, resistance to cisplatin treatment often occurs, leading to relapse. Therefore, there is a need for the development of more effective treatment strategies that can overcome chemoresistance. Myricetin is a flavonoid from fruits and vegetables, showing anticancer activity in various cancer cells. In this study, we found myricetin exhibited greater cytotoxicity than cisplatin in two cisplatin-resistant ovarian cancer cell lines, OVCAR-3 and A2780/CP70, and it was less cytotoxic to the normal ovarian cell line IOSE-364. Myricetin selectively induced apoptosis in both cisplatinresistant cancer cell lines, but did not induce apoptosis in the normal ovarian cell line. It induced both Bcl-2 familydependent intrinsic and DR5 dependent extrinsic apoptosis in OVCAR-3 cells. P53, a multifunctional tumor suppressor, regulated apoptosis in OVCAR-3 cells through a Bcl-2 family protein-dependent pathway. Myricetin did not induce cell cycle arrest in either ovarian cancer cell line. Because of its potency and selectivity against cisplatin-resistant cancer cells, myricetin could potentially be used to overcome cancer chemoresistance against platinum-based therapy

The flavonoid nobiletin inhibits tumor growth and angiogenesis of ovarian cancers via the Akt pathway

Despite its importance, the death rate of ovarian cancer has remained unchanged over the past five decades, demanding an improvement in prevention and treatment of this malignancy. With no known carcinogens, targeted prevention is currently unavailable, and efforts in early detection of this malignancy by screening biomarkers have failed. The inhibition of angiogenesis, also known as angioprevention, is a promising strategy to limit the growth of solid tumors, including ovarian cancers. Nobiletin, a polymethoxy flavonoid compound isolated from the tiansheng plant, has been shown to inhibit the growth of multiple types of human cancers. However, there are no reports involving the effect on nobiletin on human ovarian cancer. The present report shows that nobiletin potently decreases the viability of ovarian cancer cells in vitro. However, nobiletin does not affect the viability of normal ovarian epithelial cells at \u3c40 µM. The antitumor activity of nobiletin was also observed in athymic mouse models and in chicken chorioallantoic membrane (CAM) models. The anti-neoplastic activity of nobiletin was due to its ability to inhibit angiogenesis. We also studied the molecular mechanisms by which nobiletin suppresses angiogenesis. We observed that nobiletin inhibits secretion of the key angiogenesis mediators, Akt, HIF-1α, NF-κB and vascular epithelial growth factor (VEGF) by ovarian cancer cells. Transient transfection experiments showed that nobiletin inhibits production of HIF-1α by downregulation of Akt. Such decreased levels of HIF-1α were responsible for nobiletin-induced suppression of VEGF. Our data suggest that nobiletin may be a promising anti-angiogenic agent relevant for therapy of ovarian cancers

The Sonodegradation of Caffeic Acid under Ultrasound Treatment: Relation to Stability

molecule

Experimental and Theoretical Explanations for the Initial Difference in the Hydraulic Head in Aquitards

Accurate estimation of the buoyancy forces exerted on underground structures is a problem in geotechnical engineering that directly impacts the construction safety and cost of these structures. Therefore, studying the buoyancy resistance of underground structures has great scientific and practical value. In this study, an initial difference in the hydraulic head, Δh0, was discovered to be present in aquitards through analysis of water-level data collected from the observation of real-world structures and in laboratory control tests. That is, seepage occurs beyond a threshold Δh0. Analysis of test data reveals that a deviation from Darcy’s law is the theoretical basis for Δh0 and that Δh0 equals the initial hydraulic gradient multiplied by the length of the seepage path. The general consistency between the experimentally measured and theoretically calculated values of Δh0 validates the theoretical explanation for Δh0. The results of this study provide a basis for scientifically calculating the buoyancy resistance required for the construction of underground structures

Association of serum brain‐derived neurotrophic factor level and early response to antipsychotic drug in first‐episode patients with schizophrenia

Abstract Objectives To investigate the role of Brain derived neurotrophic factor (BDNF) in the psychotic symptoms in first‐episode patients with schizophrenia and whether BDNF levels were associated with the improvement of psychotic symptoms after risperidone treatment. Methods 89 schizophrenia patients and 90 healthy controls were recruited, the schizophrenia patients were assigned into early response or early non‐response groups at 2 weeks based on improvement in the positive and negative symptoms scale (PANSS) total score. All patients were treated with risperidone for 2 weeks, their serum BDNF levels were compared at baseline and after 2 weeks treatment. Results We found that patients had lower BDNF levels, compared to controls at baseline. After 2 weeks of treatment of risperidone, BDNF levels were significantly increased and psychotic symptoms were decreased in early response group. Correlation analysis showed that the change of BDNF levels after treatment was correlated with the change of PANSS total score. Further regression analysis showed that the change in BDNF levels was an independent predictor for the improvement in psychotic symptoms. Conclusions Our findings reveal that the level of BDNF was lower in first‐episode schizophrenic patients, moreover, the changes in serum BDNF levels may have a predictive effect on the early improvement in psychotic symptoms in the first 2 weeks

Proanthocyanidins from Chinese Bayberry (<i>Myrica rubra Sieb. et Zucc.</i>) Leaves Effectively Inhibit the Formation of Biogenic Amines in the Brewing Soy Sauce

Biogenic amines are a group of metabolites generated in the process of soy sauce brewing, which can result in severe negative impacts on human health at high concentrations. In this study, we innovatively proposed natural extracts (0.1 wt%), of proanthocyanidins, from Chinese bayberry (Myrica rubra Sieb. et Zucc.) leaves to alternate commercial additives (0.1 wt%), i.e., sodium benzoate and potassium sorbate, for lowering the harmful biogenic amine formation during the fermentation of soy sauce. HPLC results showed that natural extracts from Chinese bayberry leaves could effectively decrease the content of cadaverine, putrescine, histamine, tyramine, phenylethylamine, and agmatine (p p < 0.05), like soluble saltless solids, total nitrogen, and amino acid nitrogen, during the 40-day fermentation of soy sauce, whereas proanthocyanidins extracted from Chinese bayberry leaves slightly inhibited the content of ammonium salt. Thus, we can conclude that, while inhibiting the biogenic amine and ammonium salt production, extracts from Chinese bayberry leaves facilitate or maintain the production of characteristic indicators compared to commercial sodium benzoate and potassium sorbate. Taken together, natural extracts from Chinese bayberry leaves can be considered a natural additive to significantly improve the quality of traditional brewing soy sauce

Recent Advances in Non-Targeted Screening of Compounds in Plastic-Based/Paper-Based Food Contact Materials

Ensuring the safety of food contact materials has become a pressing concern in recent times. However, detecting hazardous compounds in such materials can be a complex task, and traditional screening methods may not be sufficient. Non-targeted screening technologies can provide comprehensive information on all detectable compounds, thereby supporting the identification, detection, and risk assessment of food contact materials. Nonetheless, the non-targeted screening of food contact materials remains a challenging issue. This paper presents a detailed review of non-targeted screening technologies relying on high-resolution mass spectrometry for plastic-based and paper-based food contact materials over the past five years. Methods of extracting, separating, concentrating, and enriching compounds, as well as migration experiments related to non-targeted screening, are examined in detail. Furthermore, instruments and devices of high-resolution mass spectrometry used in non-targeted screening technologies for food contact materials are discussed and summarized. The research findings aim to provide a theoretical basis and practical reference for the risk management of food contact materials and the development of relevant regulations and standards

Dietary compounds galangin and myricetin suppress ovarian cancer cell angiogenesis

Galangin and myricetin are flavonoids isolated from vegetables and fruits which exhibit anti-proliferative activity in human cancer cells. In this study, their anti-angiogenic effects were investigated with in vitro (HUVEC) and in vivo (CAM) models, which showed that galangin and myricetin inhibited angiogenesis induced by OVCAR-3 cells. The molecular mechanisms through which galangin and myricetin suppress angiogenesis were also studied. It was observed that galangin and myricetin inhibited secretion of the key angiogenesis mediator vascular endothelial growth factor (VEGF) and decreased levels of p-Akt, p-p70S6K and hypoxia-inducible factor-1α (HIF-1α) proteins in A2780/CP70 and OVCAR-3 cells. Transient transfection experiments showed that galangin and myricetin inhibited secretion of VEGF by the Akt/p70S6K/HIF-1α pathway. Moreover, a novel pathway, p21/HIF-1α/VEGF, was found to be involved in the inhibitory effect of myricetin on angiogenesis in OVCAR-3 cells. These data suggest that galangin and myricetin might serve as potential anti-angiogenic agents in the prevention of ovarian cancers dependent on new blood vessel networks

Nobiletin suppresses cell viability through AKT Pathways in PC-3 and DU-145 prostate cancer cells

Background Nobiletin is a non-toxic dietary flavonoid that possesses anti-cancer properties. Nobiletin has been reported to reduce the risk of prostate cancer, but the mechanism is not well understood. In this study, we investigated the effects of nobiletin in prostate cancer cell lines PC-3 and DU-145. Methods Nobiletin was isolated from a polymethoxy flavonoid mixture using HPLC, cell viability was analyzed with MTS-based assays. Protein expression was examined by ELISA and western blotting. Gene expression was examined by luciferase assay. And the pathways were examined by manipulating genetic components with plasmid transfection. Results Data showed that nobiletin decreased cell viability in both prostate cell lines, with a greater reduction in viability in PC-3 cells. HIF-1α expression and AKT phosphorylation were decreased in both cell lines. The VEGF expression was inhibited in PC-3 but not DU-145 cells. cMyc expression was decreased in DU-145 cells. Nobiletin down-regulated NF-κB (p50) expression in nuclei of DU145 cells but not whole cells. It also suppressed NF-κB expression in both whole cells and nuclei of PC-3 cells. Increasing HIF-1α levels reversed nobiletin’s inhibitory effects on VEGF expression, and up-regulating AKT levels reversed its inhibitory effects on HIF-1α expression. We speculate that AKT influences cell viability probably by its effect on NF-κB in both prostate cells. The effect of nobiletin on VEGF expression in PC-3 cell lines was through the AKT/HIF-1α pathway. Conclusion Taken together, our results show that nobiletin suppresses cell viability through AKT pathways, with a more profound effect against the more metastatic PC-3 line. Due to this enhanced action against a more malignant cell type, nobiletin may be used to improve prostate cancer survival rates