It is of great significance to find safe and effective radiosensitizers.A primary investigation has been made on fisetin's modification of radiation effect,but its radiosensitization and related mechanisms still n...It is of great significance to find safe and effective radiosensitizers.A primary investigation has been made on fisetin's modification of radiation effect,but its radiosensitization and related mechanisms still need to be deeply clarified.Furthermore,fisetin with high hydrophobicity is difficult to dissolve in water,severely limiting its research and application.In this study,we fabricated a safe and soluble radiosensitizer fisetin micelle for precisely enhancing radiotherapy by inhibiting platelet-derived growth factor receptor-β(PDGFRβ)/signal transducer and activator of transcription 1(STAT1)/signal transducer and activator of transcription 3(STAT3)/B cell lymphoma 2(Bcl-2)signaling pathway in the tumor.Systematic and detailed studies were performed to verify its radiosensitization effect in vitro and in vivo.On the cellular level,fisetin micelles selectively increased the radiosensitivity of tumor cells(CT26 and 4T1 cells)and had little effect on the sensitivity of normal mouse cells(L929 cells)to radiation.In the mouse models of colon and breast cancers,fisetin micelles showed an efficient radiosensitization capacity without apparent toxicity.Additionally,we first found that fisetin micelles played a radiotherapy sensitization role by inhibiting the PDGFRβ/STAT1/STAT3/Bcl-2 pathway activity.In general,this work not only confirmed that fisetin micelles precisely exhibit a radiosensitization effect in vitro and in vivo,but also profoundly explored its mechanisms underlying,to provide a theoretical and experimental basis for the clinical application of fisetin micelles.展开更多
Flavonoids,including fisetin,have been linked to a reduced risk of colorectal cancer(CRC)and have potential therapeutic applications for the condition.Fisetin,a natural flavonoid found in various fruits and vegetables...Flavonoids,including fisetin,have been linked to a reduced risk of colorectal cancer(CRC)and have potential therapeutic applications for the condition.Fisetin,a natural flavonoid found in various fruits and vegetables,has shown promise in managing CRC due to its diverse biological activities.It has been found to influence key cell signaling pathways related to inflammation,angiogenesis,apoptosis,and transcription factors.The results of this study demonstrate that fisetin induces colon cancer cell apoptosis through multiple mechanisms.It impacts the p53 pathway,leading to increased levels of p53 and decreased levels of murine double minute 2,contributing to apoptosis induction.Fisetin also triggers the release of important components in the apoptotic process,such as second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI and cytochrome c.Furthermore,fisetin inhibits the cyclooxygenase-2 and wingless-related integration site(Wnt)/epidermal growth factor receptor/nuclear factor kappa B signaling pathways,reducing Wnt target gene expression and hindering colony formation.It achieves this by regulating the activities of cyclin-dependent kinase 2 and cyclin-dependent kinase 4,reducing retinoblastoma protein phosphorylation,decreasing cyclin E levels,and increasing p21 levels,ultimately influencing E2 promoter binding factor 1 and cell division cycle 2(CDC2)protein levels.Additionally,fisetin exhibits various effects on CRC cells,including inhibiting the phosphorylation of Y-box binding protein 1 and ribosomal S6 kinase,promoting the phosphorylation of extracellular signal-regulated kinase 1/2,and disrupting the repair process of DNA double-strand breaks.Moreover,fisetin serves as an adjunct therapy for the prevention and treatment of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunitα(PIK3CA)-mutant CRC,resulting in a reduction in phosphatidylinositol-3 kinase(PI3K)expression,Ak strain transforming phosphorylation,m TOR activity,and downstream target proteins in CRC cells with a PIK3CA mutation.These findings highlight the multifaceted potential of fisetin in managing CRC and position it as a promising candidate for future therapy development.展开更多
Cellular senescence is the results of aging and age-related diseases,and the development of anti-aging methods may improve health and extend longevity.The natural flavonol fisetin has been shown to antagonize senescen...Cellular senescence is the results of aging and age-related diseases,and the development of anti-aging methods may improve health and extend longevity.The natural flavonol fisetin has been shown to antagonize senescence in vitro and increases longevity in vivo,but has poor water solubility and limited bioavailability.In this study,a food-grade and senescent cell-targeted delivery system for fisetin was developed based on whey protein isolate-galactooligosaccharides(WPI-GOS)Maillard conjugate,which could recognize senescence associatedβ-galactosidase in senescent cells.The fisetin nanoparticles possessed a high encapsulation efficiency,excellent dispersibility in water,good storage stability and well biocompatibility.Moreover,they could effectively accumulate and retain in senescent cells with excellent senescent cell-targeting efficacy,and inhibit the oxidative stress-induced cellular senescence in vitro.Thus,this novel nanoparticle system based on WPI-GOS Maillard conjugate showed promise to deliver hydrophobic bioactive ingredients like fisetin to senescent cells to improve their bioavailability and anti-senescence effect.展开更多
Background: Hepatic ischemia-reperfusion(I/R) injury(IRI) represents a crucial challenge in liver transplantation. Fisetin has anti-inflammatory, anti-aging and anti-oxidative properties. This study aimed to examine w...Background: Hepatic ischemia-reperfusion(I/R) injury(IRI) represents a crucial challenge in liver transplantation. Fisetin has anti-inflammatory, anti-aging and anti-oxidative properties. This study aimed to examine whether fisetin mitigates hepatic IRI and examine its underlying mechanisms. Methods: Sham or warm hepatic I/R operated mice were pretreated with fisetin(5, 10 or 20 mg/kg). Hepatic histological assessments, TUNEL assays and serum aminotransferase measurements were performed. An in vitro hypoxia/reoxygenation(H/R) model using RAW264.7 macrophages pretreated with fisetin(2.5, 5 or 10 μmol/L) was also used. Serum and cell supernatant concentrations of interleukin-1 β(IL-1 β), IL-18 and tumor necrosis factor-α(TNF-α) were determined by enzyme-linked immunosorbent assay(ELISA). Protein levels of p-GSK3 β, p-AMPK and NLR family pyrin domain-containing 3(NLRP3)-associated proteins were detected by Western blotting. Results: Compared with the I/R group, fisetin pretreatment reduced pathological liver damage, serum aminotransferase levels, serum concentrations of IL-1 β, IL-18 and TNF-α in the murine IRI model. Fisetin also reduced the expression of NLRP3 inflammasome-associated proteins(NLRP3, cleaved caspase-1, IL-1 β and IL-18) in I/R-operated liver. The experiments in vitro showed that fisetin decreased the release of IL-1 β, IL-18 and TNF-α, and reduced the expression of NLRP3 inflammasome-associated proteins in H/R-treated RAW264.7 cells. Moreover, fisetin increased the expressions of p-GSK3 β and p-AMPK in both models, indicating that its anti-inflammatory effects were dependent on GSK3 β/AMPK signaling. The antiinflammatory effects of fisetin were partially inhibited by the AMPK specific inhibitor compound C. Conclusions: Fisetin showed protective effects against hepatic IRI, countering inflammatory responses through mediating the GSK3 β/AMPK/NLRP3 inflammasome pathway.展开更多
OBJECTIVE This study aims to explore the anticancer effect of fisetin for breast cancer in vivo and in vitro.METHODS Viability of cultured breast cancer cells including 4T1,Mcf-7 and MDA-MB-231 were determined using M...OBJECTIVE This study aims to explore the anticancer effect of fisetin for breast cancer in vivo and in vitro.METHODS Viability of cultured breast cancer cells including 4T1,Mcf-7 and MDA-MB-231 were determined using MTT assay and electric cell-substrate impedance sensing(ECIS).Cell migratory ability was evaluated by wound healing assay.Cell apoptosis was quantified using the AnnexinⅤ/propidium iodide(PI)detection kit and analyzed by flow cytometry.Subsequently,the potential anti-tumor and anti-metastatic mechanism was investigated by Western blotting.Inhibition of tumor growth and metastasis was evaluated by assessment of tumor weight,volume and analysis of bioluminescent signal after a homograft inoculation.Oral,intraperitoneal were respectively administered in different media.RESULTS we found that fisetin inhibited the proliferation and induced apoptosis of breast cel lines.Our study showed that fisetin inhibited migration of breast cancer cells.Importantly,our data demonstrated theanticancer activity of fisetin by oral administration.In addition,the PI3K/AKT/m TORstatus in breast cancer cells may contribute to fisetin anticancer activity.CONCLUSION Fisetin exerts anti-tumor growth and anti-metastatic effects in breast cancer cells,that is,at least partly,associated with decreased downregulation of PI3K/AKT/m TOR expression,The absolute bioavailability of intraperitoneal administration is relatively lower than that of intragastric administration,the anticancer effect of fisetin in vivo needs more study to address the solubility issue.展开更多
Over the past decades,epidemiological studies have concluded that a diet rich in plant-derived products plays a pivotal role in human health.Fisetin(3,3’,4’,7-tetrahydroxyflavone)is a hydrophobic polyphenolic compou...Over the past decades,epidemiological studies have concluded that a diet rich in plant-derived products plays a pivotal role in human health.Fisetin(3,3’,4’,7-tetrahydroxyflavone)is a hydrophobic polyphenolic compound primarily found in edible plants(e.g.strawberry,blueberry,apple,grape,persimmon,kiwi,and cucumber).Various preclinical studies have revealed that fisetin exhibits a wide range of pharmacological effects such as antioxidant,antiinflammatory,anti-carcinogenic,anti-osteoporotic,antimicrobial,and anti-diabetic properties.Therefore,the pharmacological in vitro and in vivo studies on fisetin are discussed in this review.Additionally,this review would be useful for further study regarding the potential of natural products,notably fisetin,and its therapeutic potential for the prevention and treatment of diseases.展开更多
Poor prognosis is associated with oral squamous cell carcinoma(OSCC),an aggressive form of malignant tumor.1 Developing effective targeted therapies against OSCC is anticipated to have significant clinical implication...Poor prognosis is associated with oral squamous cell carcinoma(OSCC),an aggressive form of malignant tumor.1 Developing effective targeted therapies against OSCC is anticipated to have significant clinical implications.Fisetin(3,30,40,7-tetrahydroxyflavone),a natural flavonoid,the most common phytochemical found in a variety of fruits and vegetables,may bring several therapeutic potential benefits to people.2 Investigating the pharmacological impact of natural flavonoid fisetin on the management of OSCC was the aim of the current investigation.By focusing on the tumor-associated antigen MUC1(mucin 1),fisetin prevents OSCC cells from transforming malignant.This study aims to provide new diagnostic indicators and therapeutic targets for the diagnosis and treatment of OSCC by exploring the role and mechanism of fisetin in OSCC.展开更多
基金funded by a grant from Technology Project of Science and technology department of Sichuan province(No.2018SZ0021)。
文摘It is of great significance to find safe and effective radiosensitizers.A primary investigation has been made on fisetin's modification of radiation effect,but its radiosensitization and related mechanisms still need to be deeply clarified.Furthermore,fisetin with high hydrophobicity is difficult to dissolve in water,severely limiting its research and application.In this study,we fabricated a safe and soluble radiosensitizer fisetin micelle for precisely enhancing radiotherapy by inhibiting platelet-derived growth factor receptor-β(PDGFRβ)/signal transducer and activator of transcription 1(STAT1)/signal transducer and activator of transcription 3(STAT3)/B cell lymphoma 2(Bcl-2)signaling pathway in the tumor.Systematic and detailed studies were performed to verify its radiosensitization effect in vitro and in vivo.On the cellular level,fisetin micelles selectively increased the radiosensitivity of tumor cells(CT26 and 4T1 cells)and had little effect on the sensitivity of normal mouse cells(L929 cells)to radiation.In the mouse models of colon and breast cancers,fisetin micelles showed an efficient radiosensitization capacity without apparent toxicity.Additionally,we first found that fisetin micelles played a radiotherapy sensitization role by inhibiting the PDGFRβ/STAT1/STAT3/Bcl-2 pathway activity.In general,this work not only confirmed that fisetin micelles precisely exhibit a radiosensitization effect in vitro and in vivo,but also profoundly explored its mechanisms underlying,to provide a theoretical and experimental basis for the clinical application of fisetin micelles.
文摘Flavonoids,including fisetin,have been linked to a reduced risk of colorectal cancer(CRC)and have potential therapeutic applications for the condition.Fisetin,a natural flavonoid found in various fruits and vegetables,has shown promise in managing CRC due to its diverse biological activities.It has been found to influence key cell signaling pathways related to inflammation,angiogenesis,apoptosis,and transcription factors.The results of this study demonstrate that fisetin induces colon cancer cell apoptosis through multiple mechanisms.It impacts the p53 pathway,leading to increased levels of p53 and decreased levels of murine double minute 2,contributing to apoptosis induction.Fisetin also triggers the release of important components in the apoptotic process,such as second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI and cytochrome c.Furthermore,fisetin inhibits the cyclooxygenase-2 and wingless-related integration site(Wnt)/epidermal growth factor receptor/nuclear factor kappa B signaling pathways,reducing Wnt target gene expression and hindering colony formation.It achieves this by regulating the activities of cyclin-dependent kinase 2 and cyclin-dependent kinase 4,reducing retinoblastoma protein phosphorylation,decreasing cyclin E levels,and increasing p21 levels,ultimately influencing E2 promoter binding factor 1 and cell division cycle 2(CDC2)protein levels.Additionally,fisetin exhibits various effects on CRC cells,including inhibiting the phosphorylation of Y-box binding protein 1 and ribosomal S6 kinase,promoting the phosphorylation of extracellular signal-regulated kinase 1/2,and disrupting the repair process of DNA double-strand breaks.Moreover,fisetin serves as an adjunct therapy for the prevention and treatment of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunitα(PIK3CA)-mutant CRC,resulting in a reduction in phosphatidylinositol-3 kinase(PI3K)expression,Ak strain transforming phosphorylation,m TOR activity,and downstream target proteins in CRC cells with a PIK3CA mutation.These findings highlight the multifaceted potential of fisetin in managing CRC and position it as a promising candidate for future therapy development.
基金supported by Dalian Youth Science and Technology Star Project(2020RQ121)the National Science Fund for Distinguished Young Scholars of China(31925031)+1 种基金Doctoral Scientific Research Foundation of Liaoning Province(2020-BS-211)Liaoning Province Education Administration(J2020101)。
文摘Cellular senescence is the results of aging and age-related diseases,and the development of anti-aging methods may improve health and extend longevity.The natural flavonol fisetin has been shown to antagonize senescence in vitro and increases longevity in vivo,but has poor water solubility and limited bioavailability.In this study,a food-grade and senescent cell-targeted delivery system for fisetin was developed based on whey protein isolate-galactooligosaccharides(WPI-GOS)Maillard conjugate,which could recognize senescence associatedβ-galactosidase in senescent cells.The fisetin nanoparticles possessed a high encapsulation efficiency,excellent dispersibility in water,good storage stability and well biocompatibility.Moreover,they could effectively accumulate and retain in senescent cells with excellent senescent cell-targeting efficacy,and inhibit the oxidative stress-induced cellular senescence in vitro.Thus,this novel nanoparticle system based on WPI-GOS Maillard conjugate showed promise to deliver hydrophobic bioactive ingredients like fisetin to senescent cells to improve their bioavailability and anti-senescence effect.
基金This study was supported by grants from the National Natural Science Foundation of China(81672959,81873592 and 81703063)the Science and Technology Commission Foundation of Chongqing,China(cstc2019jscx-gksb X0005)+1 种基金the Natural Science Foundation of Chongqing,China(cstc2018jscx-msyb X0133)the graduate tu-tor team construction project of Chongqing Municipal Education Commission Foundation,China(dstd201801).
文摘Background: Hepatic ischemia-reperfusion(I/R) injury(IRI) represents a crucial challenge in liver transplantation. Fisetin has anti-inflammatory, anti-aging and anti-oxidative properties. This study aimed to examine whether fisetin mitigates hepatic IRI and examine its underlying mechanisms. Methods: Sham or warm hepatic I/R operated mice were pretreated with fisetin(5, 10 or 20 mg/kg). Hepatic histological assessments, TUNEL assays and serum aminotransferase measurements were performed. An in vitro hypoxia/reoxygenation(H/R) model using RAW264.7 macrophages pretreated with fisetin(2.5, 5 or 10 μmol/L) was also used. Serum and cell supernatant concentrations of interleukin-1 β(IL-1 β), IL-18 and tumor necrosis factor-α(TNF-α) were determined by enzyme-linked immunosorbent assay(ELISA). Protein levels of p-GSK3 β, p-AMPK and NLR family pyrin domain-containing 3(NLRP3)-associated proteins were detected by Western blotting. Results: Compared with the I/R group, fisetin pretreatment reduced pathological liver damage, serum aminotransferase levels, serum concentrations of IL-1 β, IL-18 and TNF-α in the murine IRI model. Fisetin also reduced the expression of NLRP3 inflammasome-associated proteins(NLRP3, cleaved caspase-1, IL-1 β and IL-18) in I/R-operated liver. The experiments in vitro showed that fisetin decreased the release of IL-1 β, IL-18 and TNF-α, and reduced the expression of NLRP3 inflammasome-associated proteins in H/R-treated RAW264.7 cells. Moreover, fisetin increased the expressions of p-GSK3 β and p-AMPK in both models, indicating that its anti-inflammatory effects were dependent on GSK3 β/AMPK signaling. The antiinflammatory effects of fisetin were partially inhibited by the AMPK specific inhibitor compound C. Conclusions: Fisetin showed protective effects against hepatic IRI, countering inflammatory responses through mediating the GSK3 β/AMPK/NLRP3 inflammasome pathway.
基金The project supported by Beijing Municipal Science and Technology Commission(D161100005116005)Beijing Municipal Education Commission(KM201510025025)+1 种基金National Natural Science Foundation of China(81173239,81373815,81202840)Specialized Research Fund for the Doctoral Program of Higher Education of China(20131107110014)
文摘OBJECTIVE This study aims to explore the anticancer effect of fisetin for breast cancer in vivo and in vitro.METHODS Viability of cultured breast cancer cells including 4T1,Mcf-7 and MDA-MB-231 were determined using MTT assay and electric cell-substrate impedance sensing(ECIS).Cell migratory ability was evaluated by wound healing assay.Cell apoptosis was quantified using the AnnexinⅤ/propidium iodide(PI)detection kit and analyzed by flow cytometry.Subsequently,the potential anti-tumor and anti-metastatic mechanism was investigated by Western blotting.Inhibition of tumor growth and metastasis was evaluated by assessment of tumor weight,volume and analysis of bioluminescent signal after a homograft inoculation.Oral,intraperitoneal were respectively administered in different media.RESULTS we found that fisetin inhibited the proliferation and induced apoptosis of breast cel lines.Our study showed that fisetin inhibited migration of breast cancer cells.Importantly,our data demonstrated theanticancer activity of fisetin by oral administration.In addition,the PI3K/AKT/m TORstatus in breast cancer cells may contribute to fisetin anticancer activity.CONCLUSION Fisetin exerts anti-tumor growth and anti-metastatic effects in breast cancer cells,that is,at least partly,associated with decreased downregulation of PI3K/AKT/m TOR expression,The absolute bioavailability of intraperitoneal administration is relatively lower than that of intragastric administration,the anticancer effect of fisetin in vivo needs more study to address the solubility issue.
文摘Over the past decades,epidemiological studies have concluded that a diet rich in plant-derived products plays a pivotal role in human health.Fisetin(3,3’,4’,7-tetrahydroxyflavone)is a hydrophobic polyphenolic compound primarily found in edible plants(e.g.strawberry,blueberry,apple,grape,persimmon,kiwi,and cucumber).Various preclinical studies have revealed that fisetin exhibits a wide range of pharmacological effects such as antioxidant,antiinflammatory,anti-carcinogenic,anti-osteoporotic,antimicrobial,and anti-diabetic properties.Therefore,the pharmacological in vitro and in vivo studies on fisetin are discussed in this review.Additionally,this review would be useful for further study regarding the potential of natural products,notably fisetin,and its therapeutic potential for the prevention and treatment of diseases.
基金supported by the National Natural Science Foundation of China(No.81902701 to Y.L.,82103649 to H.Z.)the Natural Science Foundation of Liaoning Province,China(No.20180530037 to Y.L.,2022-MS-183 to W.D.).
文摘Poor prognosis is associated with oral squamous cell carcinoma(OSCC),an aggressive form of malignant tumor.1 Developing effective targeted therapies against OSCC is anticipated to have significant clinical implications.Fisetin(3,30,40,7-tetrahydroxyflavone),a natural flavonoid,the most common phytochemical found in a variety of fruits and vegetables,may bring several therapeutic potential benefits to people.2 Investigating the pharmacological impact of natural flavonoid fisetin on the management of OSCC was the aim of the current investigation.By focusing on the tumor-associated antigen MUC1(mucin 1),fisetin prevents OSCC cells from transforming malignant.This study aims to provide new diagnostic indicators and therapeutic targets for the diagnosis and treatment of OSCC by exploring the role and mechanism of fisetin in OSCC.
