Jing Ji, Zhen Zhang, Guanrong Li, Lingyi Zuo, JIAO-JIAO Zhou, Xiu-jun Wang, SHAO-JIE Ma, Bin Liu, JIN-QING Han, Xiao Hou
The novel Abemaciclib derivative WXJ-8 may be a promising anti-tumour drug; however, its mechanism of action and clinical value need to be further verified in research. Cell cycle regulating systems are critical in parthenogenesis and progression. Because of its involvement in regulating cell cycle checkpoints, the CDK4/6-CyclinD1-Rb-E2F1 signalling pathway has been proposed as a possible therapeutic target for breast cancer. As a result, WXJ-8, a new and highly specific CDK4/6 inhibitor, was developed and synthesized in this investigation. The activity of WXJ-8 against breast cancer cells in vitro was detected by MTT method. The main subjects were MDA-MB-231 and MCF-7 cells. Plate cloning, wound healing, invasion and adhesion experiments revealed that WXJ-8 had strong anti-proliferation, migration, invasion, and adhesion effects on breast cancer cells. Protein blotting revealed significant down regulation of CDK4, CDK6, p-Rb, E2F1 and other cell cycle factors in the CDK4/6-CyclinD1-Rb-E2F1 pathway, as well as activation of Bcl-2, Caspase-3, and Cleaved Caspase-3 apoptotic factor expression, resulting in MDA-MB-231 cell cycle arrest and apoptosis. Finally, our research implies that WXJ-8 might be a potential anti-triple-negative breast cancer medication candidate.
{"title":"Novel CDK4/6 lnhibitor, WXJ-8 -Exerts Anti-effects Through Cell Cycle in Breast Cancer","authors":"Jing Ji, Zhen Zhang, Guanrong Li, Lingyi Zuo, JIAO-JIAO Zhou, Xiu-jun Wang, SHAO-JIE Ma, Bin Liu, JIN-QING Han, Xiao Hou","doi":"10.32383/appdr/173986","DOIUrl":"https://doi.org/10.32383/appdr/173986","url":null,"abstract":"The novel Abemaciclib derivative WXJ-8 may be a promising anti-tumour drug; however, its mechanism of action and clinical value need to be further verified in research. Cell cycle regulating systems are critical in parthenogenesis and progression. Because of its involvement in regulating cell cycle checkpoints, the CDK4/6-CyclinD1-Rb-E2F1 signalling pathway has been proposed as a possible therapeutic target for breast cancer. As a result, WXJ-8, a new and highly specific CDK4/6 inhibitor, was developed and synthesized in this investigation. The activity of WXJ-8 against breast cancer cells in vitro was detected by MTT method. The main subjects were MDA-MB-231 and MCF-7 cells. Plate cloning, wound healing, invasion and adhesion experiments revealed that WXJ-8 had strong anti-proliferation, migration, invasion, and adhesion effects on breast cancer cells. Protein blotting revealed significant down regulation of CDK4, CDK6, p-Rb, E2F1 and other cell cycle factors in the CDK4/6-CyclinD1-Rb-E2F1 pathway, as well as activation of Bcl-2, Caspase-3, and Cleaved Caspase-3 apoptotic factor expression, resulting in MDA-MB-231 cell cycle arrest and apoptosis. Finally, our research implies that WXJ-8 might be a potential anti-triple-negative breast cancer medication candidate.","PeriodicalId":7135,"journal":{"name":"Acta Poloniae Pharmaceutica - Drug Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139249774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Katarzyna Gawron, D. Piotrowska, G. Andrei, D. Schols, R. Snoeck, I. Głowacka
A new series of N-(diethylphosphonoalkyl)-1,8-naphthalimides were synthesized via direct reaction of 1,8-naphthalic anhydride or its 3-nitro- and 4-bromo- derivatives with selected ɷ-aminoalkylphosphonates and evaluated against a broad-spectrum of viruses as well as for their cytostatic properties toward selected cell lines. N-(diethylphosphonomethyl)-3-nitro-1,8-naphthalimide 15a exhibited inhibitory activity toward coxsackie virus B4 in Vero cells (EC50 = 9.45 μM), whereas 3-nitro-1,8-naphthalimides 15b and 15d containing short 2-carbon linker showed moderate activity against herpes simplex virus-2 (G) and herpes simplex virus-1 TK– KOS ACVr. Furthermore, compounds 15a, 15b and 15d showed antiviral potency against human coronavirus. Several naphthalimides exhibited cytostatic activity toward tested cancerous cell lines as well as normal retina cells. Transformation of selected diethyl phosphonates 13, 14 and 15 into ammonium phosphonates 21, 22 and 23 improved the solubility, however, did not result in the enhancement of antiviral and cytostatic potency of the compounds.
{"title":"Synthesis, Antiviral and Cytostatic Activity of New Series of Naphthalimide Derivatives","authors":"Katarzyna Gawron, D. Piotrowska, G. Andrei, D. Schols, R. Snoeck, I. Głowacka","doi":"10.32383/appdr/171434","DOIUrl":"https://doi.org/10.32383/appdr/171434","url":null,"abstract":"A new series of N-(diethylphosphonoalkyl)-1,8-naphthalimides were synthesized via direct reaction of 1,8-naphthalic anhydride or its 3-nitro- and 4-bromo- derivatives with selected ɷ-aminoalkylphosphonates and evaluated against a broad-spectrum of viruses as well as for their cytostatic properties toward selected cell lines. N-(diethylphosphonomethyl)-3-nitro-1,8-naphthalimide 15a exhibited inhibitory activity toward coxsackie virus B4 in Vero cells (EC50 = 9.45 μM), whereas 3-nitro-1,8-naphthalimides 15b and 15d containing short 2-carbon linker showed moderate activity against herpes simplex virus-2 (G) and herpes simplex virus-1 TK– KOS ACVr. Furthermore, compounds 15a, 15b and 15d showed antiviral potency against human coronavirus. Several naphthalimides exhibited cytostatic activity toward tested cancerous cell lines as well as normal retina cells. Transformation of selected diethyl phosphonates 13, 14 and 15 into ammonium phosphonates 21, 22 and 23 improved the solubility, however, did not result in the enhancement of antiviral and cytostatic potency of the compounds.","PeriodicalId":7135,"journal":{"name":"Acta Poloniae Pharmaceutica - Drug Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139252063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K. Kus, Maria Sygit, Maciuszek-Bartkowska Barbara, P. Ratajczak, A. Paczkowska, Dorota Kopciuch, T. Zaprutko
Medical databases are crucial tools in medicine and pharmacy, aiding studies on the impact of medical products on health and informing treatment decisions. However, prescribers must blend database insights with clinical expertise for accurate choices. Clinical experience doesn't always align with drug Summaries of Product Characteristics (SPCs). While SPC guidelines ensure safety, they might not optimize efficacy. For instance, treating Polycystic Ovary Syndrome (PCOS) often benefits from off-label therapies that are clinically and cost-effective. The study aimed to identify potential PCOS treatments beyond approved uses in Poland and globally. The methodology involved reviewing databases used by medical professionals. Out of 29, 11 databases were chosen based on off-label drug availability and relevance to PCOS. Results show that medical databases aid medical professionals in finding off-label PCOS treatments. These databases also assess a drug's potential efficacy and risks. However, their usefulness has limits, lacking comprehensive data on usage, mechanisms, and safety. When using literary databases, keyword selection significantly influences search results.
{"title":"Polycystic Ovary Syndrome (PCOS) - The Application of Selected off-label drugs found in medical databases","authors":"K. Kus, Maria Sygit, Maciuszek-Bartkowska Barbara, P. Ratajczak, A. Paczkowska, Dorota Kopciuch, T. Zaprutko","doi":"10.32383/appdr/172065","DOIUrl":"https://doi.org/10.32383/appdr/172065","url":null,"abstract":"Medical databases are crucial tools in medicine and pharmacy, aiding studies on the impact of medical products on health and informing treatment decisions. However, prescribers must blend database insights with clinical expertise for accurate choices. Clinical experience doesn't always align with drug Summaries of Product Characteristics (SPCs). While SPC guidelines ensure safety, they might not optimize efficacy. For instance, treating Polycystic Ovary Syndrome (PCOS) often benefits from off-label therapies that are clinically and cost-effective. The study aimed to identify potential PCOS treatments beyond approved uses in Poland and globally. The methodology involved reviewing databases used by medical professionals. Out of 29, 11 databases were chosen based on off-label drug availability and relevance to PCOS. Results show that medical databases aid medical professionals in finding off-label PCOS treatments. These databases also assess a drug's potential efficacy and risks. However, their usefulness has limits, lacking comprehensive data on usage, mechanisms, and safety. When using literary databases, keyword selection significantly influences search results.","PeriodicalId":7135,"journal":{"name":"Acta Poloniae Pharmaceutica - Drug Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139253803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study aimed to prepare a novel multifunctional magnetic nanoparticle (MNP) with a drug-loadable encapsulation and a matrix metalloproteinase (MMP) substrate-modified TAT peptide whose transmembrane ability can be activated in an MMP-rich environment, and to evaluate the uptake of this nanoparticle by cells, as well as its cytotoxicity. Nanoparticles were synthesized and modified with TAT or MMPs-TAT peptides. PC-3 cells and RWPE-1 cells were cultured with these nanoparticles at different concentrations, with or without MMP-2 pretreatment, and their uptake rate and toxicity were determined using flow cytometry and fluorescence microscopy. The nanoparticles were characterized with TEM (transmission electron microscopy) and DLS (dynamic light scattering). The diameter of these nanoparticles ranged from 194.5 ± 69.4 nm to 353.1 ± 103.9 nm, which were in the ideal range for application. The cellular uptake of MMPs-TAT-MNPs appeared similar to MNPs, but significantly increased in the presence of MMP-2 pretreatment. MMPs-TAT-MNPs had no significant cytotoxicity at the concentration of ≤25 μg/ml. MMPs-TAT-MNPs with MMP-2 substrate modified TAT peptide is successfully prepared, possess a low cytotoxicity loadable cargo and can be activated in an MMP-2 rich niche.
{"title":"Synthesis and Verification of a Novel Attainable Tumor Targeting Magnetic Nanoparticle","authors":"Yingxiu Chen, Jiasheng Yan","doi":"10.32383/appdr/173984","DOIUrl":"https://doi.org/10.32383/appdr/173984","url":null,"abstract":"This study aimed to prepare a novel multifunctional magnetic nanoparticle (MNP) with a drug-loadable encapsulation and a matrix metalloproteinase (MMP) substrate-modified TAT peptide whose transmembrane ability can be activated in an MMP-rich environment, and to evaluate the uptake of this nanoparticle by cells, as well as its cytotoxicity. Nanoparticles were synthesized and modified with TAT or MMPs-TAT peptides. PC-3 cells and RWPE-1 cells were cultured with these nanoparticles at different concentrations, with or without MMP-2 pretreatment, and their uptake rate and toxicity were determined using flow cytometry and fluorescence microscopy. The nanoparticles were characterized with TEM (transmission electron microscopy) and DLS (dynamic light scattering). The diameter of these nanoparticles ranged from 194.5 ± 69.4 nm to 353.1 ± 103.9 nm, which were in the ideal range for application. The cellular uptake of MMPs-TAT-MNPs appeared similar to MNPs, but significantly increased in the presence of MMP-2 pretreatment. MMPs-TAT-MNPs had no significant cytotoxicity at the concentration of ≤25 μg/ml. MMPs-TAT-MNPs with MMP-2 substrate modified TAT peptide is successfully prepared, possess a low cytotoxicity loadable cargo and can be activated in an MMP-2 rich niche.","PeriodicalId":7135,"journal":{"name":"Acta Poloniae Pharmaceutica - Drug Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139252930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Szymon Sip, P. Zalewski, J. Cielecka‐Piontek, Anna Pałubicka
This study investigated the degradation kinetics and stability of rosuvastatin calcium (RSV) in acidic and alkaline solutions at two different doses, 5 mg and 10 mg. The degradation reaction was characterised by the activation energy (Ea), enthalpy change (ΔH≠a), and entropy change (ΔS≠a). The degradation of RSV in acidic solution followed pseudo-first-order kinetics, with observed rate constants (kobs) of 2.63×10-3 s-1 and 3.80×10-3 s-1 for the 5 mg and 10 mg doses, respectively. The activation energy (Ea) was 102.1 kJ/mol and 101.8 kJ/mol for the 5 mg and 10 mg doses, respectively, indicating that the degradation process is moderately sensitive to temperature. The enthalpy change (ΔH≠a) for both doses was positive, with values of 92 kJ/mol and 102 kJ/mol for the 5 mg and 10 mg doses, respectively, indicating that the degradation reaction is endothermic, with the 5 mg dose requiring more significant heat input. The entropy change (ΔS≠a) for both doses was negative, with values of -0.219 kJ/(mol∙K) and -0.236 kJ/(mol∙K) for the 5 mg and 10 mg doses, respectively, indicating that the degradation process decreases the system's disorder, with the 5 mg dose having a more significant impact. The degradation of RSV in an alkaline medium was found to be a pseudo-first-order reaction, with observed rate constants ranging from 1.98×10-3 s-1 to 7.09×10-3 s-1, depending on the RSV concentration. The results suggest that higher RSV concentrations improve stability in alkaline conditions. These findings provide valuable insights into the stability of RSV under different pH conditions.
{"title":"Stability of API as a Key Parameter for New Formulations Development - A Case Study of Rosuvastatin Calcium","authors":"Szymon Sip, P. Zalewski, J. Cielecka‐Piontek, Anna Pałubicka","doi":"10.32383/appdr/174028","DOIUrl":"https://doi.org/10.32383/appdr/174028","url":null,"abstract":"This study investigated the degradation kinetics and stability of rosuvastatin calcium (RSV) in acidic and alkaline solutions at two different doses, 5 mg and 10 mg. The degradation reaction was characterised by the activation energy (Ea), enthalpy change (ΔH≠a), and entropy change (ΔS≠a). The degradation of RSV in acidic solution followed pseudo-first-order kinetics, with observed rate constants (kobs) of 2.63×10-3 s-1 and 3.80×10-3 s-1 for the 5 mg and 10 mg doses, respectively. The activation energy (Ea) was 102.1 kJ/mol and 101.8 kJ/mol for the 5 mg and 10 mg doses, respectively, indicating that the degradation process is moderately sensitive to temperature. The enthalpy change (ΔH≠a) for both doses was positive, with values of 92 kJ/mol and 102 kJ/mol for the 5 mg and 10 mg doses, respectively, indicating that the degradation reaction is endothermic, with the 5 mg dose requiring more significant heat input. The entropy change (ΔS≠a) for both doses was negative, with values of -0.219 kJ/(mol∙K) and -0.236 kJ/(mol∙K) for the 5 mg and 10 mg doses, respectively, indicating that the degradation process decreases the system's disorder, with the 5 mg dose having a more significant impact. The degradation of RSV in an alkaline medium was found to be a pseudo-first-order reaction, with observed rate constants ranging from 1.98×10-3 s-1 to 7.09×10-3 s-1, depending on the RSV concentration. The results suggest that higher RSV concentrations improve stability in alkaline conditions. These findings provide valuable insights into the stability of RSV under different pH conditions.","PeriodicalId":7135,"journal":{"name":"Acta Poloniae Pharmaceutica - Drug Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139251078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Hur, Sanghee Kim, Bo-ra Yoon, Guijae Yoo, In-Hae Choi, Ho-Young Park, Sang Yoon Choi
Obesity is caused by excessive adipogenesis and leads to metabolic diseases such as diabetes, hypertension, and degenerative arthritis. Therefore, there is an ever-increasing need to identify new anti-obesity compounds. In this study, the anti-obesity effects of (E)-3-(4-(tert-butyl)phenyl)-N-isobutyl-2-methylacrylamide (BPIMA) were evaluated using pre-adipocytes and a high-fat-fed C57BL/6J mouse model. As the results, BPIMA effectively inhibited adipocyte differentiation (64.3% at 40 μM) without exhibiting any cytotoxicity. Additionally, BPIMA decreased the protein levels of PPARγ, FAS, C/EBP, and SREBP in 3T3-L1 cells in a concentration-dependent manner. In C57BL/6J mice, a significant decrease in body weight, adipose tissue, and fatty liver was observed in the BPIMA-treated high-fat group compared to that observed in the vehicle-treated high-fat group; the serum levels of total cholesterol and glucose also significantly decreased in the BPIMA-treated high-fat group. Moreover, the weight and fat level of liver and serum AST, ALT activity in the BPIMA-treated high-fat group were similar to low fat diet-control group. These findings show that BPIMA may be a potential anti-obesity compound.
{"title":"(E)-3-(4-(tert-Butyl)Phenyl)-N-Isobutyl-2-Methylacrylamide Suppresses Adipogenesis in High-Fat-Fed Mice","authors":"J. Hur, Sanghee Kim, Bo-ra Yoon, Guijae Yoo, In-Hae Choi, Ho-Young Park, Sang Yoon Choi","doi":"10.32383/appdr/171509","DOIUrl":"https://doi.org/10.32383/appdr/171509","url":null,"abstract":"Obesity is caused by excessive adipogenesis and leads to metabolic diseases such as diabetes, hypertension, and degenerative arthritis. Therefore, there is an ever-increasing need to identify new anti-obesity compounds. In this study, the anti-obesity effects of (E)-3-(4-(tert-butyl)phenyl)-N-isobutyl-2-methylacrylamide (BPIMA) were evaluated using pre-adipocytes and a high-fat-fed C57BL/6J mouse model. As the results, BPIMA effectively inhibited adipocyte differentiation (64.3% at 40 μM) without exhibiting any cytotoxicity. Additionally, BPIMA decreased the protein levels of PPARγ, FAS, C/EBP, and SREBP in 3T3-L1 cells in a concentration-dependent manner. In C57BL/6J mice, a significant decrease in body weight, adipose tissue, and fatty liver was observed in the BPIMA-treated high-fat group compared to that observed in the vehicle-treated high-fat group; the serum levels of total cholesterol and glucose also significantly decreased in the BPIMA-treated high-fat group. Moreover, the weight and fat level of liver and serum AST, ALT activity in the BPIMA-treated high-fat group were similar to low fat diet-control group. These findings show that BPIMA may be a potential anti-obesity compound.","PeriodicalId":7135,"journal":{"name":"Acta Poloniae Pharmaceutica - Drug Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139252053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tong Chen, Pan-Pan Wei, Mengyue Deng, Yuzhen Ding, Die Xia, Zijun Yan
Oxidative stress is associated with the development of many diseases, such as chronic inflammation, cardiovascular disease and cancer. Antioxidants can scavenge free radicals in the body, reduce the production of reactive oxygen species (ROS) and effectively prevent oxidative stress. Polysaccharide is a antioxidants that widely found in natural resources, which is a kind of high molecular polymer with antioxidant activity. It can prevent oxidative stress and play a role in disease prevention through various mechanisms. In this paper, the different types of polysaccharides were summarized, such as plant polysaccharides, algal polysaccharides, microbial polysaccharides and animal polysaccharides, and their antioxidant mechanism and application in the treatment of disease were also discussed. we hope this review can offer some theoretical basis and inspiration for the antioxidant activity study and application of polysaccharides from natural resources.
{"title":"Antioxidant Activity of Polysaccharides From Natural Sources","authors":"Tong Chen, Pan-Pan Wei, Mengyue Deng, Yuzhen Ding, Die Xia, Zijun Yan","doi":"10.32383/appdr/173189","DOIUrl":"https://doi.org/10.32383/appdr/173189","url":null,"abstract":"Oxidative stress is associated with the development of many diseases, such as chronic inflammation, cardiovascular disease and cancer. Antioxidants can scavenge free radicals in the body, reduce the production of reactive oxygen species (ROS) and effectively prevent oxidative stress. Polysaccharide is a antioxidants that widely found in natural resources, which is a kind of high molecular polymer with antioxidant activity. It can prevent oxidative stress and play a role in disease prevention through various mechanisms. In this paper, the different types of polysaccharides were summarized, such as plant polysaccharides, algal polysaccharides, microbial polysaccharides and animal polysaccharides, and their antioxidant mechanism and application in the treatment of disease were also discussed. we hope this review can offer some theoretical basis and inspiration for the antioxidant activity study and application of polysaccharides from natural resources.","PeriodicalId":7135,"journal":{"name":"Acta Poloniae Pharmaceutica - Drug Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139250907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Doxorubicin (DOX) still remains one the most effective a clinical drug for breast cancer treatment. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the n-3 polyunsaturated fatty acids (PUFAs), exert pronounced toxicity against many types of cancers including breast cancer. That is why it was decided to investigate the mechanism of DOX and PUFAs toxicity on SK-BR-3 and MDA-MB-231 cells. The influence of DOX on the PUFAs oxidation and effect of DOX and EPA or DHA on cellular metabolic activity, viability, cytotoxicity, apoptosis and oxidative DNA damage in these cells were measured. DOX induced oxidation of the EPA and DHA. Toxicity of DOX and PUFAs towards breast cancer cells was associated with oxidative damage. These PUFAs reduced growth of the tested cells and caused their death. EPA and DHA potentiated DOX toxic effects through induction of oxidative DNA damage. The antitumor effect of PUFAs alone and combined with DOX strongly depended on induction of the oxidative stress that facilitated cell death. The observed changes of DOX toxicity induced by PUFAs suggest the possibility of their application in developing therapeutic anticancer strategies.
多柔比星（DOX）仍然是治疗乳腺癌最有效的临床药物之一。二十碳五烯酸（EPA）和二十二碳六烯酸（DHA），即 n-3 多不饱和脂肪酸（PUFAs），对包括乳腺癌在内的多种癌症具有明显的毒性。因此，我们决定研究 DOX 和 PUFA 对 SK-BR-3 和 MDA-MB-231 细胞的毒性机制。研究人员测定了 DOX 对 PUFAs 氧化的影响，以及 DOX 和 EPA 或 DHA 对这些细胞的代谢活性、存活率、细胞毒性、细胞凋亡和 DNA 氧化损伤的影响。DOX 诱导了 EPA 和 DHA 的氧化。DOX 和 PUFA 对乳腺癌细胞的毒性与氧化损伤有关。这些 PUFAs 可降低受测细胞的生长速度并导致其死亡。EPA 和 DHA 通过诱导氧化 DNA 损伤增强了 DOX 的毒性作用。PUFAs 单独或与 DOX 合用的抗肿瘤效果在很大程度上取决于氧化应激的诱导，而氧化应激可促进细胞死亡。观察到的 PUFAs 诱导的 DOX 毒性变化表明，它们有可能被应用于开发抗癌治疗策略。
{"title":"Interaction of PUFAs and Doxorubicin: the Enhanced Toxicity in Breast Cancer Cells","authors":"A. Zajdel, A. Wilczok","doi":"10.32383/appdr/171546","DOIUrl":"https://doi.org/10.32383/appdr/171546","url":null,"abstract":"Doxorubicin (DOX) still remains one the most effective a clinical drug for breast cancer treatment. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the n-3 polyunsaturated fatty acids (PUFAs), exert pronounced toxicity against many types of cancers including breast cancer. That is why it was decided to investigate the mechanism of DOX and PUFAs toxicity on SK-BR-3 and MDA-MB-231 cells. The influence of DOX on the PUFAs oxidation and effect of DOX and EPA or DHA on cellular metabolic activity, viability, cytotoxicity, apoptosis and oxidative DNA damage in these cells were measured. DOX induced oxidation of the EPA and DHA. Toxicity of DOX and PUFAs towards breast cancer cells was associated with oxidative damage. These PUFAs reduced growth of the tested cells and caused their death. EPA and DHA potentiated DOX toxic effects through induction of oxidative DNA damage. The antitumor effect of PUFAs alone and combined with DOX strongly depended on induction of the oxidative stress that facilitated cell death. The observed changes of DOX toxicity induced by PUFAs suggest the possibility of their application in developing therapeutic anticancer strategies.","PeriodicalId":7135,"journal":{"name":"Acta Poloniae Pharmaceutica - Drug Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139253776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Agnieszka Zakrzeska, P. Kitlas, A. Shlyahtun, Natalia Szymańska, Ryszard Jabłoński, M. Tomulewicz
Betulin is natural pentacyclic triterpenoids lupane-structure, which shows a wide range of biological activity, including possibly hypoglycemic effects. Diabetes mellitus is a metabolic disease, accompanied by chronic hyperglycemia caused by absolute or relative insulin deficiency. The main effective drug in the treatment of type 1 diabetes is insulin injections. In the case of type 2 diabetes, it is an adjuvant therapy. To purpose of this study was to show hypoglycemic action of betulin in a model of experimentally induced diabetes in rats. For the induction of diabetes, alloxan at a dose of 170 mg/kg, i.p. was used. The hypoglycemic effect of betulin was evaluated using doses of 50 and 100 mg/kg/day for 30 days. The activity of glucose metabolism enzymes: liver glycogen phosphorylase, hexokinase and liver and skeletal muscle phosphofructokinase in rats, glucose-6-phosphate dehydrogenase (DG-6-P) of the liver was also evaluated. Betulin in a dose-dependent manner normalized of glycemia, increased the basal insulin concentration in the blood serum, increased the activity of carbohydrate metabolizing enzymes and on the gene expression profile of enzymes involved in carbohydrate metabolism. Betulin also significant improved the morphology of the pancreas. In particular, there was an increase in the area of the islands, their diameter, an increase in the number of β cells in the composition of the islands. We conclude that betulin has hypoglycemic properties, improving glycemia and carbohydrate metabolizing enzymes and pancreatic morphology.
{"title":"Hypoglycemic Effect of Betulin in Rats With Experimental Diabetes","authors":"Agnieszka Zakrzeska, P. Kitlas, A. Shlyahtun, Natalia Szymańska, Ryszard Jabłoński, M. Tomulewicz","doi":"10.32383/appdr/172620","DOIUrl":"https://doi.org/10.32383/appdr/172620","url":null,"abstract":"Betulin is natural pentacyclic triterpenoids lupane-structure, which shows a wide range of biological activity, including possibly hypoglycemic effects. Diabetes mellitus is a metabolic disease, accompanied by chronic hyperglycemia caused by absolute or relative insulin deficiency. The main effective drug in the treatment of type 1 diabetes is insulin injections. In the case of type 2 diabetes, it is an adjuvant therapy. To purpose of this study was to show hypoglycemic action of betulin in a model of experimentally induced diabetes in rats. For the induction of diabetes, alloxan at a dose of 170 mg/kg, i.p. was used. The hypoglycemic effect of betulin was evaluated using doses of 50 and 100 mg/kg/day for 30 days. The activity of glucose metabolism enzymes: liver glycogen phosphorylase, hexokinase and liver and skeletal muscle phosphofructokinase in rats, glucose-6-phosphate dehydrogenase (DG-6-P) of the liver was also evaluated. Betulin in a dose-dependent manner normalized of glycemia, increased the basal insulin concentration in the blood serum, increased the activity of carbohydrate metabolizing enzymes and on the gene expression profile of enzymes involved in carbohydrate metabolism. Betulin also significant improved the morphology of the pancreas. In particular, there was an increase in the area of the islands, their diameter, an increase in the number of β cells in the composition of the islands. We conclude that betulin has hypoglycemic properties, improving glycemia and carbohydrate metabolizing enzymes and pancreatic morphology.","PeriodicalId":7135,"journal":{"name":"Acta Poloniae Pharmaceutica - Drug Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139251045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A good understanding of the physico-chemical characteristics of a drug substance and excipients is necessary to obtain a safe and effective drug dosage form. Based on the current recommendations of the regulatory agencies (EMA, FDA) regarding the implementation of the Quality by Design concept at the drug product development stage, this article is focused on the application of the experimental design approach at the preformulation studies. The purpose of this work was the implementation of experimental design methodology in a compatibility study between ketoprofen (non-steroidal anti-inflammatory drug) and selected solid dosage forms excipients. The fractional factorial design was used to generate a matrix of multi-component mixtures of ketoprofen and selected excipients. In order to accelerate any chemical incompatibilities, the received mixtures were exposed to elevated temperature and humidity (60°C/75% RH) in a climate chamber for 3 weeks. The ketoprofen-excipients compatibility was studied by means of the RP-HPLC method. It was confirmed that the type of disintegrant had a strong impact on ketoprofen degradation. The incompatibility in mixtures of ketoprofen with sodium starch glycolate was indicated. According to literature data, it may be the result of a decrease in crystallinity and thus a decrease in the stability of ketoprofen in the presence of sodium starch glycolate. The effects of the other types of excipients were statistically insignificant (p > 0.05). The applied experimental design methodology allowed for a rational selection of optimal excipients and thus, this approach may support significantly decision-making in the pharmaceutical industry.
{"title":"Compatibility Study of Ketoprofen With Selected Excipients Used in Solid Dosage Forms: Experimental Design Approach","authors":"Joanna Ronowicz-Pilarczyk","doi":"10.32383/appdr/172622","DOIUrl":"https://doi.org/10.32383/appdr/172622","url":null,"abstract":"A good understanding of the physico-chemical characteristics of a drug substance and excipients is necessary to obtain a safe and effective drug dosage form. Based on the current recommendations of the regulatory agencies (EMA, FDA) regarding the implementation of the Quality by Design concept at the drug product development stage, this article is focused on the application of the experimental design approach at the preformulation studies. The purpose of this work was the implementation of experimental design methodology in a compatibility study between ketoprofen (non-steroidal anti-inflammatory drug) and selected solid dosage forms excipients. The fractional factorial design was used to generate a matrix of multi-component mixtures of ketoprofen and selected excipients. In order to accelerate any chemical incompatibilities, the received mixtures were exposed to elevated temperature and humidity (60°C/75% RH) in a climate chamber for 3 weeks. The ketoprofen-excipients compatibility was studied by means of the RP-HPLC method. It was confirmed that the type of disintegrant had a strong impact on ketoprofen degradation. The incompatibility in mixtures of ketoprofen with sodium starch glycolate was indicated. According to literature data, it may be the result of a decrease in crystallinity and thus a decrease in the stability of ketoprofen in the presence of sodium starch glycolate. The effects of the other types of excipients were statistically insignificant (p > 0.05). The applied experimental design methodology allowed for a rational selection of optimal excipients and thus, this approach may support significantly decision-making in the pharmaceutical industry.","PeriodicalId":7135,"journal":{"name":"Acta Poloniae Pharmaceutica - Drug Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139252354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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