Cysteine cathepsins are important regulators and signaling molecules of an unimaginable number of biological processes, while they concurrently play an essential role in cancer progression, invasion and metastasis. Th...Cysteine cathepsins are important regulators and signaling molecules of an unimaginable number of biological processes, while they concurrently play an essential role in cancer progression, invasion and metastasis. The purposes of our study were to: a) compare the expression levels of cathepsins B, H and L in the supernatants of colon cancer tissues from 74 patients versus the corresponding enzymic expressions of supernatants in the adjacent normal colorectal tissues;and b) correlate our results to the grade of the malignancy by using an enzyme-linked immunosorbent assay (ELISA). The findings indicated that cathepsins B, H and L of all malignant tissues exhibited significantly higher expression levels than their corresponding controls. Furthermore, cathepsin B expression levels doubled in all tumor samples and this increase remained quite steady with tumor stage advancement, in contrast to cathepsin H expression which rose significantly as malignancy progressed. Specifically, cathepsin H concentration was higher than the corresponding control: 155% in B1 stage and 204.44% in D stage. Among the three investigated proteases, cathepsin L has shown the highest increase, which in D stage stood 261.03% higher than the corresponding control. The results at hand suggested that cysteine protease H and L expression levels could be of critical value in the diagnosis and progression of colon cancer.展开更多
AIM: To examine the effectiveness of human placental inhibitors, by injecting vitamin E to rats with transplanted Morris-5123 hepatoma, on the expression of cathepsins B and L in tumor, liver, lung and blood sera afte...AIM: To examine the effectiveness of human placental inhibitors, by injecting vitamin E to rats with transplanted Morris-5123 hepatoma, on the expression of cathepsins B and L in tumor, liver, lung and blood sera after transplantation of Morris 5123 hepatoma. METHODS: Animals were divided into 10 groups receiving three different concentrations of vitamin E and inhibitors along or in combination and compared with negative control (healthy rats) and positive control (tumor rats). Effectiveness of treatment was evaluated with regard to survival time, tumor response and determination of the activities of proteolytic enzymes and their inhibitors using flurogenic substrates. RESULTS: Cathepsins B and L activities were elevated by 16-fold in comparison with negative control tissues, and their endogenous inhibitor activity decreased by 1.2-fold before treatment. In several cases, tumors completely disappeared following vitamin E plus human placental cyteine protease inhibitor (CPI) compared with controls. The number of complete tumor responses was higher when 20 m/kg vitamin E plus 400 μg of CPI was used, i.e. 7/10 rats survived more than two mo. Cathepsins B and L were expressed significantly in tumor, liver, lung tissues and sera in parallel to the increasing of the endogenous inhibitor activity compared with the controls after treatment(P<0.0001) CONCLUSION: The data indicate formation of metastasis significantly reduced in treated rats, which might provide a therapeutic basis for anti-cancer therapy.展开更多
Cathepsins are highly expressed in various human cancers, associated with tumor metastasis. It is superfamily, concluding A, B, C, D, E, F, G, H, L, K, O, S, V, and W family members. As a group of lysosomal proteinase...Cathepsins are highly expressed in various human cancers, associated with tumor metastasis. It is superfamily, concluding A, B, C, D, E, F, G, H, L, K, O, S, V, and W family members. As a group of lysosomal proteinases or endopeptidases, each member has a different function, playing different roles in distinct tumorigenic processes such as proliferation, angiogenesis, metastasis, and invasion. Cathepsins belong to a diverse number of enzyme subtypes, including cysteine proteases, serine proteases and aspartic proteases. The contribution of cathepsins to invasion in human cancers is well documented, although the precise mechanisms by which cathepsins exert their effects are still not clear. In the present review, the role of cathepsin family members in cancer is discussed.展开更多
Proteases comprise a variety of enzymes defined by their ability to catalytically hydrolyze the peptide bonds of other proteins,resulting in protein lysis.Cathepsins,specifically,encompass a class of at least twenty p...Proteases comprise a variety of enzymes defined by their ability to catalytically hydrolyze the peptide bonds of other proteins,resulting in protein lysis.Cathepsins,specifically,encompass a class of at least twenty proteases with potent endopeptidase activity.They are located subcellularly in lysosomes,organelles responsible for the cell’s degradative and autophagic processes,and are vital for normal lysosomal function.Although cathepsins are involved in a multitude of cell signaling activities,this chapter will focus on the role of cathepsins(with a special emphasis on Cathepsin B)in neuronal plasticity.We will broadly define what is known about regulation of cathepsins in the central nervous system and compare this with their dysregulation after injury or disease.Importantly,we will delineate what is currently known about the role of cathepsins in axon regeneration and plasticity after spinal cord injury.It is well established that normal cathepsin activity is integral to the function of lysosomes.Without normal lysosomal function,autophagy and other homeostatic cellular processes become dysregulated resulting in axon dystrophy.Furthermore,controlled activation of cathepsins at specialized neuronal structures such as axonal growth cones and dendritic spines have been positively implicated in their plasticity.This chapter will end with a perspective on the consequences of cathepsin dysregulation versus controlled,localized regulation to clarify how cathepsins can contribute to both neuronal plasticity and neurodegeneration.展开更多
To regulate the sodium chloride content in Jinhua ham,the impact of NaCl on the activity and conformation of cathepsin B was investigated using spectroscopy and computational methods.The results showed that the activi...To regulate the sodium chloride content in Jinhua ham,the impact of NaCl on the activity and conformation of cathepsin B was investigated using spectroscopy and computational methods.The results showed that the activity of cathepsin B decreased with an increase in Na^(+)cation content and temperature.Additionally,decreasedα-helix content and increasedβ-sheet content were observed.The increase in sulfhydryl group content was attributed to the breaking of original disulfide bonds in the molecular structure or the release of embedded groups.Furthermore,the surface hydrophobicity gradually declined,which was consistent with the analysis of endogenous fluorescence spectroscopy.At the molecular level,the number of hydrogen bonds formed in NaCl-treated samples decreased,and the interactions between the hydrogen bonding were less powerful,which caused instability in the binding of the protein and substrate.The conformation of cathepsin B accurately characterized its activity,and the structural changes had a macroscopic effect on the decrease in protease activity.展开更多
The incorporation of SAEW and SI can effectively maintain the characteristics of texture in marine fish.This study aimed to investigate the relevance of cathepsin activity for texture and the establishment of a shelf-...The incorporation of SAEW and SI can effectively maintain the characteristics of texture in marine fish.This study aimed to investigate the relevance of cathepsin activity for texture and the establishment of a shelf-life model of mackerel(Pneumatophorus japonicus)stored at 4◦C.Before the cold storage,mackerel samples were exposed to flake ice(Control),slurry ice(SI),and slightly acidic electrolyzed water-slurry ice(SAEW-SI),respectively.Then the TVC,K-value,cathepsin activity,texture,and sensory attributes were investigated.The results showed that the TVC and K-value of samples in SAEW-SI group was significantly lower by approximately 1 log CFU/g and 17%than those in Control group(P<0.05).Meanwhile,there was a tendency to first increase and then decrease on the activities of cathepsin B,D and L.Results of texture profile analysis(TPA)clarified that SAEW-SI can markedly suppress the decrease of hardness,springiness and chewiness(P<0.05).During the experimental period,the highest sensory scores were obtained in SAEW-SI group.In addition,the heat map of correlation analysis suggested that texture attributes(hardness)were negatively correlated with cathepsin B(r=-0.66),cathepsin D(r=-0.49),and cathepsin L(r=-0.69),respectively.According to the principal component analysis(PCA)and analysis of linear regression,SAEW-SI treatment could effectively maintain mackerel quality and extend the estimated shelf-life of mackerel by at least 5 days compared to Control group.Therefore,SAEW-SI could be suggested as a novel strategy for cold-chain transportation in seafood industry.展开更多
Many aquatic products have been stored using superchilling technology, but rarely used for the storage of sturgeon fillets. In this study, we investigated the effects of protein oxidation, cathepsin, and various freez...Many aquatic products have been stored using superchilling technology, but rarely used for the storage of sturgeon fillets. In this study, we investigated the effects of protein oxidation, cathepsin, and various freezing temperatures on the quality of superchilled sturgeon fillets. Sensory evaluation results showed that the sensory attributes of superchilled (−3 °C) sturgeon fillets were acceptable three times longer (18 days) than samples stored at refrigeration temperatures (4 °C). The sarcoplasmic protein, carbonyl, myofibrillar protein, total sulfhydryl content and the surface hydrophobicity were determined using fluorescence spectrophotometry and SDS-PAGE. Results showed that superchilling might protect myofibrillar proteins from oxidation compared to refrigeration temperatures. The activity of the three cathepsins (B, L, and H) in terms of myofibrillar, mitochondria, lysosomes, and sarcoplasm demonstrated that superchilling can inhibit cathepsins activity in sturgeon and protect its muscle structure. Microscopic observations showed that as the temperature decreased, the gap area of the muscle fibers decreased, and the deformation of cross-sectional slices was gradually reduced. In addition, the freezing rate of ice crystals produced during the freezing process influenced the muscle structure, texture, and sensory attributes. Superchilled sturgeon fillets showed good hardness, chewiness, and water retention. In conclusion, superchilling technology shows promise for its ability to extend the shelf life while maintaining the texture and sensory attributes of fresh sturgeon fillets.展开更多
Osteoclast is critical in skeletal development and fracture healing,yet the impact and underlying mechanisms of their metabolic state on these processes remain unclear.Here,by using osteoclast-specific small GTPase Rh...Osteoclast is critical in skeletal development and fracture healing,yet the impact and underlying mechanisms of their metabolic state on these processes remain unclear.Here,by using osteoclast-specific small GTPase Rheb1-knockout mice,we reveal that mitochondrial respiration,rather than glycolysis,is essential for cathepsin K(CTSK)production in osteoclasts and is regulated by Rheb1 in a mechanistic target of rapamycin complex 1(mTORC1)-independent manner.展开更多
Pancreatitis is a common,life-threatening inflammatory disease of the exocrine pancreas.Its pathogenesis remains obscure,and no specific or effective treatment is available.Gallstones and alcohol excess are major etio...Pancreatitis is a common,life-threatening inflammatory disease of the exocrine pancreas.Its pathogenesis remains obscure,and no specific or effective treatment is available.Gallstones and alcohol excess are major etiologies of pancreatitis;in a small portion of patients the disease is hereditary.Pancreatitis is believed to be initiated by injured acinar cells(the main exocrine pancreas cell type),leading to parenchymal necrosis and local and systemic inflammation.The primary function of these cells is to produce,store,and secrete a variety of enzymes that break down all categories of nutrients.Most digestive enzymes,including all proteases,are secreted by acinar cells as inactive proforms(zymogens)and in physiological conditions are only activated when reaching the intestine.The generation of trypsin from inactive trypsinogen in the intestine plays a critical role in physiological activation of other zymogens.It was proposed that pancreatitis results from proteolytic autodigestion of the gland,mediated by premature/inappropriate trypsinogen activation within acinar cells.The intra-acinar trypsinogen activation is observed in experimental models of acute and chronic pancreatitis,and in human disease.On the basis of these observations,it has been considered the central pathogenic mechanism of pancreatitis-a concept with a century-old history.This review summarizes the data on trypsinogen activation in experimental and genetic rodent models of pancreatitis,particularly the more recent genetically engineered mouse models that mimic mutations associated with hereditary pancreatitis;analyzes the mechanisms mediating trypsinogen activation and protecting the pancreas against its’damaging effects;discusses the gaps in our knowledge,potential therapeutic approaches,and directions for future research.We conclude that trypsin is not the culprit in the disease pathogenesis but,at most,a mediator of some pancreatitis responses.Therefore,the search for effective therapies should focus on approaches to prevent or normalize other intra-acinar pathologic processes,such as defective autophagy leading to parenchymal cell death and unrelenting inflammation.展开更多
Objective:To examine the effect of icariin plus curcumol on prostate cancer cells PC3 and elucidate the underlying mechanisms.Methods:We employed the Cell Counting Kit 8 assay and colony formation assay to assess cell...Objective:To examine the effect of icariin plus curcumol on prostate cancer cells PC3 and elucidate the underlying mechanisms.Methods:We employed the Cell Counting Kit 8 assay and colony formation assay to assess cell viability and proliferation.Autophagy expression was analyzed using monodansylcadaverine staining.Immunofluorescence and Western blot analyses were used to evaluate protein expressions related to autophagy,pyroptosis,and the mTOR pathway.Cellular damage was examined using the lactate dehydrogenase assay.Moreover,cathepsin B and NLRP3 were detected by co-immunoprecipitation.Results:Icariin plus curcumol led to a decrease in PC3 cell proliferation and an enhancement of autophagy.The levels of LC3-Ⅱ/LC3-Ⅰand beclin-1 were increased,while the levels of p62 and mTOR were decreased after treatment with icariin plus curcumol.These changes were reversed upon overexpression of mTOR.Furthermore,3-methyladenine resulted in a decrease in inflammatory cytokines,pyroptosis-related protein levels,and lactate dehydrogenase concentration,compared to the icariin plus curcumol group.Inhibiting cathepsin B reversed the regulatory effects of icariin plus curcumol.Conclusions:Icariin plus curcumol demonstrates great potential as a therapeutic agent for castration-resistant prostate cancer by enhancing autophagy via the mTOR pathway and promoting pyroptosis mediated by cathepsin B.These findings provide valuable insights into the molecular mechanisms underlying the therapeutic potential of icariin and curcumol for prostate cancer treatment.展开更多
文摘Cysteine cathepsins are important regulators and signaling molecules of an unimaginable number of biological processes, while they concurrently play an essential role in cancer progression, invasion and metastasis. The purposes of our study were to: a) compare the expression levels of cathepsins B, H and L in the supernatants of colon cancer tissues from 74 patients versus the corresponding enzymic expressions of supernatants in the adjacent normal colorectal tissues;and b) correlate our results to the grade of the malignancy by using an enzyme-linked immunosorbent assay (ELISA). The findings indicated that cathepsins B, H and L of all malignant tissues exhibited significantly higher expression levels than their corresponding controls. Furthermore, cathepsin B expression levels doubled in all tumor samples and this increase remained quite steady with tumor stage advancement, in contrast to cathepsin H expression which rose significantly as malignancy progressed. Specifically, cathepsin H concentration was higher than the corresponding control: 155% in B1 stage and 204.44% in D stage. Among the three investigated proteases, cathepsin L has shown the highest increase, which in D stage stood 261.03% higher than the corresponding control. The results at hand suggested that cysteine protease H and L expression levels could be of critical value in the diagnosis and progression of colon cancer.
文摘AIM: To examine the effectiveness of human placental inhibitors, by injecting vitamin E to rats with transplanted Morris-5123 hepatoma, on the expression of cathepsins B and L in tumor, liver, lung and blood sera after transplantation of Morris 5123 hepatoma. METHODS: Animals were divided into 10 groups receiving three different concentrations of vitamin E and inhibitors along or in combination and compared with negative control (healthy rats) and positive control (tumor rats). Effectiveness of treatment was evaluated with regard to survival time, tumor response and determination of the activities of proteolytic enzymes and their inhibitors using flurogenic substrates. RESULTS: Cathepsins B and L activities were elevated by 16-fold in comparison with negative control tissues, and their endogenous inhibitor activity decreased by 1.2-fold before treatment. In several cases, tumors completely disappeared following vitamin E plus human placental cyteine protease inhibitor (CPI) compared with controls. The number of complete tumor responses was higher when 20 m/kg vitamin E plus 400 μg of CPI was used, i.e. 7/10 rats survived more than two mo. Cathepsins B and L were expressed significantly in tumor, liver, lung tissues and sera in parallel to the increasing of the endogenous inhibitor activity compared with the controls after treatment(P<0.0001) CONCLUSION: The data indicate formation of metastasis significantly reduced in treated rats, which might provide a therapeutic basis for anti-cancer therapy.
基金Supported by National Natural Science Foundation of China,No.81071718,No.81000881,No.81372282 and No.30973400Fundamental Research Funds for the Central Universities,No.21611612+1 种基金Guangdong Natural Science Foundation,No.S2013010013360the Foundation of State Key Laboratory of Oncology in South China,No.HN2011-04
文摘Cathepsins are highly expressed in various human cancers, associated with tumor metastasis. It is superfamily, concluding A, B, C, D, E, F, G, H, L, K, O, S, V, and W family members. As a group of lysosomal proteinases or endopeptidases, each member has a different function, playing different roles in distinct tumorigenic processes such as proliferation, angiogenesis, metastasis, and invasion. Cathepsins belong to a diverse number of enzyme subtypes, including cysteine proteases, serine proteases and aspartic proteases. The contribution of cathepsins to invasion in human cancers is well documented, although the precise mechanisms by which cathepsins exert their effects are still not clear. In the present review, the role of cathepsin family members in cancer is discussed.
基金JS was funded by NINDS(NS25713)Brumagin-Nelson Fund+1 种基金Kaneko Family Fundthe Hong Kong Spinal Cord Injury Fund.
文摘Proteases comprise a variety of enzymes defined by their ability to catalytically hydrolyze the peptide bonds of other proteins,resulting in protein lysis.Cathepsins,specifically,encompass a class of at least twenty proteases with potent endopeptidase activity.They are located subcellularly in lysosomes,organelles responsible for the cell’s degradative and autophagic processes,and are vital for normal lysosomal function.Although cathepsins are involved in a multitude of cell signaling activities,this chapter will focus on the role of cathepsins(with a special emphasis on Cathepsin B)in neuronal plasticity.We will broadly define what is known about regulation of cathepsins in the central nervous system and compare this with their dysregulation after injury or disease.Importantly,we will delineate what is currently known about the role of cathepsins in axon regeneration and plasticity after spinal cord injury.It is well established that normal cathepsin activity is integral to the function of lysosomes.Without normal lysosomal function,autophagy and other homeostatic cellular processes become dysregulated resulting in axon dystrophy.Furthermore,controlled activation of cathepsins at specialized neuronal structures such as axonal growth cones and dendritic spines have been positively implicated in their plasticity.This chapter will end with a perspective on the consequences of cathepsin dysregulation versus controlled,localized regulation to clarify how cathepsins can contribute to both neuronal plasticity and neurodegeneration.
基金supported by the National Natural Science Foundation of China(31972097)Jiangsu Key Research and Development Plan(Modern Agriculture)(BE2020302)+1 种基金the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(24KJB550003)2024 Huaiyin Institute of Technology Talent Recruitment Research Startup Fund Project(Z301B24521)。
文摘To regulate the sodium chloride content in Jinhua ham,the impact of NaCl on the activity and conformation of cathepsin B was investigated using spectroscopy and computational methods.The results showed that the activity of cathepsin B decreased with an increase in Na^(+)cation content and temperature.Additionally,decreasedα-helix content and increasedβ-sheet content were observed.The increase in sulfhydryl group content was attributed to the breaking of original disulfide bonds in the molecular structure or the release of embedded groups.Furthermore,the surface hydrophobicity gradually declined,which was consistent with the analysis of endogenous fluorescence spectroscopy.At the molecular level,the number of hydrogen bonds formed in NaCl-treated samples decreased,and the interactions between the hydrogen bonding were less powerful,which caused instability in the binding of the protein and substrate.The conformation of cathepsin B accurately characterized its activity,and the structural changes had a macroscopic effect on the decrease in protease activity.
基金supported by China Agriculture Research System of MOF and MARA(CARS-47)the National Key R&D Program of China(2019YFD0901602)Ability promotion project of Shanghai Municipal Science and Technology Commission Engineering Center(19DZ2284000).
文摘The incorporation of SAEW and SI can effectively maintain the characteristics of texture in marine fish.This study aimed to investigate the relevance of cathepsin activity for texture and the establishment of a shelf-life model of mackerel(Pneumatophorus japonicus)stored at 4◦C.Before the cold storage,mackerel samples were exposed to flake ice(Control),slurry ice(SI),and slightly acidic electrolyzed water-slurry ice(SAEW-SI),respectively.Then the TVC,K-value,cathepsin activity,texture,and sensory attributes were investigated.The results showed that the TVC and K-value of samples in SAEW-SI group was significantly lower by approximately 1 log CFU/g and 17%than those in Control group(P<0.05).Meanwhile,there was a tendency to first increase and then decrease on the activities of cathepsin B,D and L.Results of texture profile analysis(TPA)clarified that SAEW-SI can markedly suppress the decrease of hardness,springiness and chewiness(P<0.05).During the experimental period,the highest sensory scores were obtained in SAEW-SI group.In addition,the heat map of correlation analysis suggested that texture attributes(hardness)were negatively correlated with cathepsin B(r=-0.66),cathepsin D(r=-0.49),and cathepsin L(r=-0.69),respectively.According to the principal component analysis(PCA)and analysis of linear regression,SAEW-SI treatment could effectively maintain mackerel quality and extend the estimated shelf-life of mackerel by at least 5 days compared to Control group.Therefore,SAEW-SI could be suggested as a novel strategy for cold-chain transportation in seafood industry.
基金financial support from the Key Laboratory of Aquatic Product Processing,Ministry of Agriculture,P.R.China(NYJG201901)Natural Science Foundation of Shandong Province(ZR2019MC014)+1 种基金China Agriculture Research System of MOF and MARA(CARS-46)Jiangsu Provincial Science and Technology Program(LYG-SZ201815).
文摘Many aquatic products have been stored using superchilling technology, but rarely used for the storage of sturgeon fillets. In this study, we investigated the effects of protein oxidation, cathepsin, and various freezing temperatures on the quality of superchilled sturgeon fillets. Sensory evaluation results showed that the sensory attributes of superchilled (−3 °C) sturgeon fillets were acceptable three times longer (18 days) than samples stored at refrigeration temperatures (4 °C). The sarcoplasmic protein, carbonyl, myofibrillar protein, total sulfhydryl content and the surface hydrophobicity were determined using fluorescence spectrophotometry and SDS-PAGE. Results showed that superchilling might protect myofibrillar proteins from oxidation compared to refrigeration temperatures. The activity of the three cathepsins (B, L, and H) in terms of myofibrillar, mitochondria, lysosomes, and sarcoplasm demonstrated that superchilling can inhibit cathepsins activity in sturgeon and protect its muscle structure. Microscopic observations showed that as the temperature decreased, the gap area of the muscle fibers decreased, and the deformation of cross-sectional slices was gradually reduced. In addition, the freezing rate of ice crystals produced during the freezing process influenced the muscle structure, texture, and sensory attributes. Superchilled sturgeon fillets showed good hardness, chewiness, and water retention. In conclusion, superchilling technology shows promise for its ability to extend the shelf life while maintaining the texture and sensory attributes of fresh sturgeon fillets.
基金supported by Grant Nos.31872799,82070906 and 31701033 from the National Natural Science Foundation of ChinaGrant Nos.2020A1515011189 from Guangdong Basic and Applied Basic Research Foundation of China。
文摘Osteoclast is critical in skeletal development and fracture healing,yet the impact and underlying mechanisms of their metabolic state on these processes remain unclear.Here,by using osteoclast-specific small GTPase Rheb1-knockout mice,we reveal that mitochondrial respiration,rather than glycolysis,is essential for cathepsin K(CTSK)production in osteoclasts and is regulated by Rheb1 in a mechanistic target of rapamycin complex 1(mTORC1)-independent manner.
文摘Pancreatitis is a common,life-threatening inflammatory disease of the exocrine pancreas.Its pathogenesis remains obscure,and no specific or effective treatment is available.Gallstones and alcohol excess are major etiologies of pancreatitis;in a small portion of patients the disease is hereditary.Pancreatitis is believed to be initiated by injured acinar cells(the main exocrine pancreas cell type),leading to parenchymal necrosis and local and systemic inflammation.The primary function of these cells is to produce,store,and secrete a variety of enzymes that break down all categories of nutrients.Most digestive enzymes,including all proteases,are secreted by acinar cells as inactive proforms(zymogens)and in physiological conditions are only activated when reaching the intestine.The generation of trypsin from inactive trypsinogen in the intestine plays a critical role in physiological activation of other zymogens.It was proposed that pancreatitis results from proteolytic autodigestion of the gland,mediated by premature/inappropriate trypsinogen activation within acinar cells.The intra-acinar trypsinogen activation is observed in experimental models of acute and chronic pancreatitis,and in human disease.On the basis of these observations,it has been considered the central pathogenic mechanism of pancreatitis-a concept with a century-old history.This review summarizes the data on trypsinogen activation in experimental and genetic rodent models of pancreatitis,particularly the more recent genetically engineered mouse models that mimic mutations associated with hereditary pancreatitis;analyzes the mechanisms mediating trypsinogen activation and protecting the pancreas against its’damaging effects;discusses the gaps in our knowledge,potential therapeutic approaches,and directions for future research.We conclude that trypsin is not the culprit in the disease pathogenesis but,at most,a mediator of some pancreatitis responses.Therefore,the search for effective therapies should focus on approaches to prevent or normalize other intra-acinar pathologic processes,such as defective autophagy leading to parenchymal cell death and unrelenting inflammation.
基金supported by Natural Science Foundation of Hunan Province(No.2023JJ40511)Excellent Youth Project of Scientific Research Program of Hunan Education Department(No.22B0370)+2 种基金Project of Traditional Chinese Medicine Administration of Hunan Province(No.B2023034)Science and Technology Development Foundation of Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University(No.LYYB202214)Hunan Provincial Hygiene and Health Commission Health Research Project(No.W20243165).
文摘Objective:To examine the effect of icariin plus curcumol on prostate cancer cells PC3 and elucidate the underlying mechanisms.Methods:We employed the Cell Counting Kit 8 assay and colony formation assay to assess cell viability and proliferation.Autophagy expression was analyzed using monodansylcadaverine staining.Immunofluorescence and Western blot analyses were used to evaluate protein expressions related to autophagy,pyroptosis,and the mTOR pathway.Cellular damage was examined using the lactate dehydrogenase assay.Moreover,cathepsin B and NLRP3 were detected by co-immunoprecipitation.Results:Icariin plus curcumol led to a decrease in PC3 cell proliferation and an enhancement of autophagy.The levels of LC3-Ⅱ/LC3-Ⅰand beclin-1 were increased,while the levels of p62 and mTOR were decreased after treatment with icariin plus curcumol.These changes were reversed upon overexpression of mTOR.Furthermore,3-methyladenine resulted in a decrease in inflammatory cytokines,pyroptosis-related protein levels,and lactate dehydrogenase concentration,compared to the icariin plus curcumol group.Inhibiting cathepsin B reversed the regulatory effects of icariin plus curcumol.Conclusions:Icariin plus curcumol demonstrates great potential as a therapeutic agent for castration-resistant prostate cancer by enhancing autophagy via the mTOR pathway and promoting pyroptosis mediated by cathepsin B.These findings provide valuable insights into the molecular mechanisms underlying the therapeutic potential of icariin and curcumol for prostate cancer treatment.
