Iranian Journal of Pharmaceutical Research最新文献

{"title":"The Effect of Intrauterine Administration of Growth Hormone on IVF Success Rate in Recurrent Implantation Failure Women: A Randomized Clinical Trial.","authors":"Fatemeh Amirkhanloo, Mohammad Javanbakht, Sarah Lotfi, Ghazal Sahraiyan, Razieh Akbari, Elham Feizabad, Shima Rahimi, Mahbod Ebrahimi, Firouzeh Akbari Asbagh, Fateme Davari Tanha","doi":"10.5812/ijpr-153636","DOIUrl":"10.5812/ijpr-153636","url":null,"abstract":"<p><strong>Background: </strong>The positive effects of growth hormone (GH) on the endometrium, including increased endometrial blood supply and enhanced expression of cytokines associated with endometrial receptivity, have been noted. However, data on the effect of GH on the endometrium remain limited.</p><p><strong>Objectives: </strong>This study aimed to investigate the effect of intrauterine administration of GH on the IVF success rate in women with recurrent implantation failure (RIF).</p><p><strong>Methods: </strong>This randomized double-blind clinical trial was conducted on 60 infertile women under 40 years old with a Body Mass Index (BMI) below 30 kg/m², all diagnosed with RIF-defined as at least three failed pregnancies after transferring a minimum of four good-quality embryos due to unknown causes. Women with uterine malformations, Asherman syndrome, cavity-distorting lesions, severe endometriosis, or other underlying diseases were excluded. After six days of estrogen therapy, transvaginal ultrasound (TVS) was performed to measure and compare the thickness and quality of the endometrium. Participants were divided into two groups. In the intervention group, 10 units of GH were administered using an IUI catheter positioned one centimeter above the cervical os. Study outcomes included changes in endometrial thickness (ET) and quality, as well as pregnancy rates. Primary endpoints were changes in ET and quality, while secondary endpoints were pregnancy rates. Adverse drug responses were also evaluated.</p><p><strong>Results: </strong>The mean age was 34.96 ± 4.04 years, and the mean BMI was 24.89 ± 2.91 kg/m², with no significant differences in baseline variables between the study groups. The average ET on the 8th day of the cycle was 5.38 ± 0.96 mm in the intervention group and 5.20 ± 0.80 mm in the control group, showing no significant difference (P = 0.467). The ET on the day of initiating progesterone was 7.60 ± 1.03 mm in the intervention group and 7.40 ± 0.60 mm in the control group, with no significant difference (P = 0.264). The odds ratio for achieving a high-quality endometrium was 2.37 (95% CI 0.80 - 6.98, P = 0.116) for the GH group compared to the non-GH group. The odds ratio for achieving a clinical pregnancy was 3.06 (95% CI 0.54 - 17.37, P = 0.205) for the GH group compared to the non-GH group. Two cases of cervicitis were reported in the GH group.</p><p><strong>Conclusions: </strong>Intrauterine administration of GH appears to enhance endometrial receptivity in women with RIF.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e153636"},"PeriodicalIF":1.8,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Oral Nano-Silymarin Formulation Efficacy in the Prevention of Hand-Foot Syndrome and Neuropathy Induced by XELOX or m-FOLFOX6 Regimens in Metastatic Colorectal Cancer: A Triple-Blinded, Randomized Clinical Trial.","authors":"Hedyieh Karbasforooshan, Hossein Rahimi, Omid Arasteh, Abolghasem Allahyari, Mehdi Varmaghani, Mahdi Jannati, Vahid Ghavami, Mahmoodreza Jaafari, Sepideh Elyasi","doi":"10.5812/ijpr-152364","DOIUrl":"10.5812/ijpr-152364","url":null,"abstract":"<p><strong>Background: </strong>Folinic acid, fluorouracil, and oxaliplatin (FOLFOX) and oxaliplatin and capecitabine (XELOX) are the most widely used chemotherapy regimens for treating metastatic colorectal carcinoma (CRC). These regimens are associated with various adverse reactions, including neuropathy and hand-foot syndrome (HFS). Silymarin, a flavonoid derived from <i>Silybum marianum</i>, has a wide range of biological activities. It has been used to counteract chemotherapy side effects due to its antioxidant, anti-apoptotic, and anti-inflammatory properties.</p><p><strong>Objectives: </strong>The purpose of this study was to assess the preventive effect of nano-silymarin on neuropathy and HFS induced by the FOLFOX6 and XELOX regimens.</p><p><strong>Methods: </strong>A randomized, triple-blinded, placebo-controlled clinical trial was conducted on 60 patients who were randomly assigned to receive 70 mg capsules containing 15% silymarin nano micelles twice a day after meals, starting from the first day of the first chemotherapy course and continuing for six courses of the XELOX or m-FOLFOX6 regimen. The severity of adverse effects was assessed after the third and sixth courses based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.</p><p><strong>Results: </strong>The median CTCAE scores for HFS and neuropathy were significantly lower in the nano-silymarin group at the end of the third course (P < 0.001). However, the difference remained significant only for HFS at the end of the sixth course (P = 0.022). Additionally, the scores increased significantly in both the placebo and nano-silymarin groups during the therapy (P < 0.05).</p><p><strong>Conclusions: </strong>Nano-silymarin may be considered an adjuvant medication for the prevention of certain chemotherapy-induced adverse reactions. Further research with larger sample sizes and various doses of nano-silymarin is recommended for a more comprehensive evaluation.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e152364"},"PeriodicalIF":1.8,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual Modulation of Canonical and Non-canonical TGF-β/ROS/Erk1/2 Pathways: Synergistic Activation of Nrf-2 and Antioxidant Enzymes (SOD1, GPx, HO-1) by Quercetin Loaded in Solid Lipid Nanoparticles and Curcumin in Atherosclerosis Therapy.","authors":"Masoumeh Shamsi, Ghorban Mohammadzadeh, Mahdi Hatami, Mohammadreza Roshanazadeh, Mojgan Noor-Behbahani, Mojtaba Rashidi","doi":"10.5812/ijpr-151428","DOIUrl":"10.5812/ijpr-151428","url":null,"abstract":"<p><strong>Background: </strong>Atherosclerosis remains the leading cause of mortality worldwide, highlighting the urgent need for innovative treatments targeting chronic inflammation. Recent research indicates that quercetin (QCT) and curcumin, two naturally occurring compounds, have potential therapeutic benefits in cardiovascular diseases.</p><p><strong>Objectives: </strong>This study focuses on the novel synthesis of nano-quercetin (N-QCT) encapsulated in solid lipid nanoparticles (SLNs) and investigates the synergistic cardioprotective effects of N-QCT and curcumin on human vascular smooth muscle cells (VSMCs). The underlying molecular mechanisms, particularly the involvement of the TGF-β signaling pathway in VSMCs, are explored.</p><p><strong>Methods: </strong>The VSMCs, including TGF-β-stimulated VSMCs, were treated with N-QCT, curcumin, or a combination of both. The MTT assay was performed to evaluate the cytotoxic effects of these treatments. The cytotoxicity of various concentrations of curcumin and QCT was used to calculate the Combination Index (CI), with CI analysis quantifying synergy or antagonism. Furthermore, following TGF-β stimulation, antioxidant enzyme activity, nuclear transcription factor erythroid 2-related factor (Nrf2) mRNA expression, reactive oxygen species (ROS) production, NADPH oxidases (NOX) expression, and extracellular signal-regulated kinase (Erk)1/2 phosphorylation were measured in the treated VSMCs.</p><p><strong>Results: </strong>The N-QCT and curcumin significantly influenced Nrf2 mRNA expression and upregulated downstream antioxidant enzymes, including HO-1, GPx, and SOD1. The combination treatment further enhanced Nrf2 protein expression and modulated Erk1/2 phosphorylation. Notably, the synergistic effect of the combination produced pronounced cardioprotective outcomes, characterized by reduced ROS production and decreased phosphorylation of Erk1/2 via the TGF-β/NOX/Erk1/2 and ROS/Nrf2 signaling pathways.</p><p><strong>Conclusions: </strong>The findings demonstrate that the combination of QCT encapsulated in SLNs and curcumin synergistically reduces oxidative stress and inflammation in TGF-β-stimulated VSMCs. This effect is achieved through the inhibition of ROS/Erk1/2 signaling and the activation of Nrf2 and antioxidant enzymes. These natural compounds, when used together, represent a promising therapeutic approach for mitigating the inflammatory processes associated with atherosclerosis.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e151428"},"PeriodicalIF":1.8,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictive Insights Into Bioactive Compounds from Streptomyces as Inhibitors of SARS-CoV-2 Mutant Strains by Receptor Binding Domain: Molecular Docking and Dynamics Simulation Approaches.","authors":"Hourieh Kalhor, Mohammad Hossein Mokhtarian, Hamzeh Rahimi, Behzad Shahbazi, Reyhaneh Kalhor, Tahereh Komeili Movahed, Hoda Abolhasani","doi":"10.5812/ijpr-150879","DOIUrl":"10.5812/ijpr-150879","url":null,"abstract":"<p><strong>Background: </strong>The receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 interacts with the angiotensin-converting enzyme 2 (ACE2) receptor in humans. To date, numerous SARS-CoV-2 variants, particularly those involving mutations in the RBD, have been identified. These variants exhibit differences in transmission, pathogenicity, diagnostics, and vaccine efficacy.</p><p><strong>Objectives: </strong>Although therapeutic agents are currently available to inhibit SARS-CoV-2, most provide supportive and symptomatic relief. Moreover, different variants may exhibit resistance to these treatments. This study aimed to identify a potential compound with favorable antiviral effects against SARS-CoV-2 variants.</p><p><strong>Methods: </strong>The study explored drug discovery through structure-based virtual screening of natural products (NPs) from the StreptomeDB database, targeting the ACE2-binding pocket of the SARS-CoV-2 RBD protein. The analysis included the wild-type protein (PDB ID: 6VW1) as well as the Alpha, Beta, Delta, Lambda, Omicron/BA.1, and Omicron/BA.2 variants.</p><p><strong>Results: </strong>In silico screening identified 'Stambomycin B' as a potential compound with the highest binding affinity. Molecular dynamics simulations of the complexes, conducted over 100 ns, confirmed the prediction that 'Stambomycin B' could inhibit different SARS-CoV-2 variants effectively.</p><p><strong>Conclusions: </strong>This study concludes that 'Stambomycin B', a macrolide compound produced by <i>Streptomyces ambofaciens</i>, may be a candidate NP for effectively combating all mutants that occur in the binding of SARS-CoV-2 RBD to ACE2, even those that may arise in the future.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e150879"},"PeriodicalIF":1.8,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pethidine, Maybe a Rearrangement in the Pharmaceutical Group Is Needed!","authors":"Reza Aminnejad, Ali Solhpour, Sahar Kavousi Sisi","doi":"10.5812/ijpr-156667","DOIUrl":"10.5812/ijpr-156667","url":null,"abstract":"","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e156667"},"PeriodicalIF":1.8,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulating the Biliverdin Reductase (BVR)/ERK1/2 Axis to Attenuate Oxidative Stress in Rat Arterial Rings.","authors":"Kuldeepak Sharma, Mateja Skufca Sterle, Hugon Mozina","doi":"10.5812/ijpr-156828","DOIUrl":"10.5812/ijpr-156828","url":null,"abstract":"<p><strong>Background: </strong>Biliverdin reductase (BVR) plays a central role in bile pigment metabolism by reducing biliverdin (BV) to bilirubin (BR), a potent antioxidant that scavenges reactive oxygen species (ROS) under normal and pathological conditions. Elevated oxidative stress activates extracellular signal-regulated protein kinases 1/2 (ERK1/2) signaling, which strongly interacts with BVR's C and D motifs, forming the BVR/ERK1/2 axis. In pathological states, increased ERK1/2 activity inhibits BVR's ability to convert BV to BR, exacerbating oxidative damage and contributing to cardiovascular disease. Therefore, the interaction between BVR and ERK1/2 is critical in modulating oxidative stress.</p><p><strong>Objectives: </strong>This study aimed to evaluate the effects of BR and the ERK1/2 inhibitor PD-98059, both individually and in combination, on ROS levels, ERK1/2 activity, and vascular responses under normoxic and hypoxia-reoxygenation (H-R) injury conditions.</p><p><strong>Methods: </strong>Aortic rings from rats were subjected to equal distending pressure after oxidative stress induction using 22'-Azobis (2-amidinopropane) dihydrochloride (ABAP) in an organ bath. Different doses of BR were administered in combination with the ERK1/2 inhibitor PD-98059 to assess their impact on ROS depletion, vascular relaxation, and maximal effect (Emax).</p><p><strong>Results: </strong>The combination of BR and PD-98059 significantly enhanced aortic relaxation and Emax under both normoxic and H/R conditions compared to either treatment alone. Inhibiting ERK1/2 with PD-98059 appeared to upregulate BVR activity, increasing BR synthesis and reducing oxidative damage in aortic rings.</p><p><strong>Conclusions: </strong>Biliverdin reductase plays a vital role in defending against oxidative stress and endothelial dysfunction through its dual-specificity kinase activity and interaction with ERK1/2. ERK1/2 inhibition further enhances BR's ROS-scavenging ability and vascular protective effects. Targeting the interaction between BVR and ERK1/2 holds potential as an effective therapeutic strategy for conditions characterized by excessive ROS levels, such as cardiovascular diseases.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e156828"},"PeriodicalIF":1.8,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum for Ruthenium (II) Complexes Based on Phenanthroline-Tetrazole as Possible Anticancer Agents [Iran J Pharm Res. 2023;22(1): e136738].","authors":"Saeid Abaspour, Behzad Soltani, Hamed Hamishehkar, Moayad Hossaini Sadr","doi":"10.5812/ijpr-157768","DOIUrl":"10.5812/ijpr-157768","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.5812/ijpr-136738.].</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e157768"},"PeriodicalIF":1.8,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Application of Machine Learning in Predicting the Permeability of Drugs Across the Blood Brain Barrier.","authors":"Sogand Jafarpour, Maryam Asefzadeh, Ehsan Aboutaleb","doi":"10.5812/ijpr-149367","DOIUrl":"10.5812/ijpr-149367","url":null,"abstract":"<p><p>The inefficiency of some medications to cross the blood-brain barrier (BBB) is often attributed to their poor physicochemical or pharmacokinetic properties. Recent studies have demonstrated promising outcomes using machine learning algorithms to predict drug permeability across the BBB. In light of these findings, our study was conducted to explore the potential of machine learning in predicting the permeability of drugs across the BBB. We utilized the B3DB dataset, a comprehensive BBB permeability molecular database, to build machine learning models. The dataset comprises 7,807 molecules, including information on their permeability, stereochemistry, and physicochemical properties. After preprocessing and cleaning, various machine learning algorithms were implemented using the Python library Pycaret to predict permeability. The extra trees classifier model outperformed others when using Morgan fingerprints and Mordred chemical descriptors (MCDs), achieving an area under the curve (AUC) of 0.93 and 0.95 on the test dataset. Additionally, we conducted an experiment to train a voting classifier combining the top three performing models. The best-blended model, trained on MCDs, achieved an AUC of 0.96. Furthermore, Shapley additive exPlanations (SHAP) analysis was applied to our best-performing single model, the extra trees classifier trained on MCDs, identifying the Lipinski rule of five as the most significant feature in predicting BBB permeability. In conclusion, our combined model trained on MCDs achieved an AUC of 0.96, an F1 Score of 0.91, and an MCC of 0.74. These results are consistent with prior studies on CNS drug permeability, highlighting the potential of machine learning in this domain.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e149367"},"PeriodicalIF":1.8,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Malleatin A and B: New Premyrsine-Type Diterpenes from <i>Euphorbia malleata</i> with Cytotoxic Effects Against A2780 Wild and A2780 R-CIS Ovarian Cancer Cell Lines in Mono or Combination Treatment with Cisplatin.","authors":"Behzad Zolfaghari, Forough Akbari, Sajad Esmaeili, Mahmoud Aghaei, Fatemeh Mosaffa, Seyedeh Sara Ghorbanhosseini, Mustafa Ghanadian","doi":"10.5812/ijpr-147396","DOIUrl":"10.5812/ijpr-147396","url":null,"abstract":"<p><strong>Background: </strong>This study focused on macrocyclic diterpenes derived from Euphorbia, particularly myrsinanes, and their potential in cytotoxic and combination treatments for resistant cancer cells. We examine premyrsinanes isolated from <i>Euphorbia malleata</i> and explore their cytotoxic properties.</p><p><strong>Methods: </strong><i>Euphorbia malleata</i> was collected from Taragh-Roud, Natanz, Iran. The semi-polar chloroform/acetone extract was chromatographed and fractionated using a large silica column. Fractions containing diterpene resonances were selected based on ¹H-NMR spectra and were further subjected to smaller silica or Sephadex columns, followed by a recycling HPLC system. The isolated compounds were identified through 1D and 2D-NMR experiments and mass spectrometry. The cytotoxicity of the isolated compounds was assessed using the MTT assay against A2780 wild and A2780 cisplatin-resistant (R-CIS) cells, both in mono and combination treatments with cisplatin.</p><p><strong>Results and conclusions: </strong>Using a Waters 616 HPLC pump and a YMC prep silica column, we successfully isolated two new premyrsinane diterpenes (Malleatin A and Malleatin B) alongside two known compounds (beta-sitosterol and loliolide). Malleatin A exhibited cytotoxicity against A2780 wild and A2780 R-CIS cells, with an IC₅₀ range of 50 - 65 μM in the MTT assay. While cisplatin demonstrated significant cytotoxic effects on the A2780 wild cell line, it was ineffective against the A2780 R-CIS cells due to their resistance. However, the combination therapy of Malleatin A and cisplatin exhibited a synergistic effect, significantly increasing the mortality rate of the resistant cells compared to monotherapy. The Combination Index (CI) of 0.58 indicates effective synergy, and the Dose Reduction Index (DRI) of 3.65 suggests a favorable reduction in the dosage of cisplatin needed, potentially reducing its associated side effects.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e147396"},"PeriodicalIF":1.8,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of Apoptosis, Autophagy, and Metastasis by Luteolin in Human Bladder Cancer EJ138 Cells: An Experimental Study.","authors":"Mohammad Amin Vatankhah, Alireza Ziyabakhsh, Mohammad Vakili Ojarood","doi":"10.5812/ijpr-153408","DOIUrl":"10.5812/ijpr-153408","url":null,"abstract":"<p><strong>Background: </strong>Chemotherapy remains a primary approach to cancer treatment, widely applied in bladder cancer (BC). However, the various side effects and resistance associated with chemotherapeutic drugs pose significant challenges in BC therapy, prompting interest in natural compounds like luteolin. Studies focus on its effects on key biological processes involved in BC, including metastasis, apoptosis, and autophagy.</p><p><strong>Objectives: </strong>This study investigated the regulation of mRNA expression of genes associated with apoptosis (BCL2, P53), autophagy (ULK1, ATG12), and metastasis (MMP2, MMP9) in malignant BC cells treated with luteolin.</p><p><strong>Methods: </strong>This was an in vitro experimental study. EJ138 BC cells were treated with various concentrations of luteolin, and its impact on cell viability, proliferation, and gene expression was assessed.The cytotoxic effect of luteolin on EJ138 BC cells was evaluated using the MTT assay after 24- and 48-hour treatments with different luteolin concentrations. Flow cytometry was performed to examine luteolin's anti-proliferative effect, and RT-PCR was used to analyze mRNA expression of BCL2, P53, ULK1, ATG12, MMP2, and MMP9 genes.</p><p><strong>Results: </strong>MTT assay results confirmed that luteolin reduced the proliferation rate of BC cells. Flow cytometry indicated increased cell death in EJ138 BC cells following luteolin treatment. RT-PCR findings demonstrated that luteolin upregulated P53, ULK1, and ATG12 expression while downregulating BCL2 mRNA expression. However, luteolin treatment in EJ138 cells did not significantly alter MMP2 and MMP9 expression levels.</p><p><strong>Conclusions: </strong>These findings indicate that luteolin exerts cytotoxic effects on EJ138 BC cells by dysregulating mRNA expression of genes involved in apoptosis and autophagy. Therefore, luteolin shows potential as an effective anti-cancer agent for BC therapy.</p>","PeriodicalId":14595,"journal":{"name":"Iranian Journal of Pharmaceutical Research","volume":"23 1","pages":"e153408"},"PeriodicalIF":1.8,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}