Current cancer drug targets最新文献

{"title":"Silencing HEATR1 Rescues Cisplatin Resistance of Non-Small Cell Lung Cancer by Inducing Ferroptosis via the p53/SAT1/ALOX15 Axis.","authors":"Xing Ma, Yifan Gan, Zhongchao Mai, Yanan Song, Miao Zhang, Wei Xia","doi":"10.2174/0115680096284068240506095417","DOIUrl":"https://doi.org/10.2174/0115680096284068240506095417","url":null,"abstract":"<p><strong>Background: </strong>Cisplatin (DDP) is a commonly used chemotherapy agent. However, its resistance to the drug is a major challenge in its clinical application. Earlier research has suggested a connection between HEATR1 and chemoresistance in cancer. However, additional investigation is needed to better understand its involvement in resistance to DDP. In this study, we aimed to determine the regulatory effect of HEATR1 on the resistance of cisplatin in NSCLC.</p><p><strong>Methods: </strong>We collected specimens of both DDP-resistant and non-resistant NSCLC to examine the expression of HEATR1. Additionally, we established cisplatin-resistant cells of NSCLC using the A549 cell line. Cell ability was examined by CCK-8 assay. Cell apoptosis and lipid ROS were examined by flow cytometry. The expressions of HEATR1, p53, SAT1, and ALOX15 were determined by qRT-PCR and Western blot. The tumor xenograft experiment was conducted to assess the impact of silencing HEATR1 on cisplatin resistance in vivo in NSCLC.</p><p><strong>Results: </strong>The expression levels of HEATR1 were found to be significantly elevated in DDP-resistant tissues and cells of NSCLC as compared to non-resistant counterparts. Conversely, the expression levels of p53, SAT1, and ALOX15 were observed to be reduced in DDP-resistant cells. Through the inhibition of HEATR1, the proliferation of DDP-resistant cells was significantly suppressed, while the generation of lipid ROS was enhanced. This effect was achieved by activating ferroptosis and the p53/SAT1/ALOX15 pathway, as demonstrated both in vitro and in vivo. Conversely, the overexpression of HEATR1 exhibited opposite effects. Furthermore, the silencing of p53 and ALOX15 reversed the oncogenic effects of HEATR1 and inhibited ferroptosis in DDP-resistant NSCLC cells, suggesting the involvement of p53 and ALOX15 in HEATR1-mediated DDP resistance.</p><p><strong>Conclusion: </strong>Finally, the findings revealed that HEATR1 silencing reduced DDP resistance in NSCLC by inducing ferroptosis via the p53/SAT1/ALOX15 axis. HEATR1 might become a potential target for overcoming DDP resistance in NSCLC treatment.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Potential of Nano Pharmaceuticals to Change the Paradigm of Brain Tumor Therapy: A State-of-the-Art Review.","authors":"Abeer Zahid, Zeinab Hammoud, Solay Farhat, Oroshay Kaiwan, Yana Al-Inaya, Viviana Cortiana, Bhavya Pahwa, Hitesh Chopra, Mayur Parmar, Mohammad Amjad Kamal, Yashendra Sethi","doi":"10.2174/0115680096286740240507092553","DOIUrl":"https://doi.org/10.2174/0115680096286740240507092553","url":null,"abstract":"<p><p>Central nervous system tumors are abnormal proliferations of neuronal cells within the brain and spinal cord. They can be primary or secondary and place a heavy financial, psychological, and physical burden on individuals. The highly selective blood-brain barrier, which only permits specific molecules to flow into the brain parenchyma, inhibits the efficacy of pharmacological medicines. Treatment options include surgery, chemoradiotherapy, and targeted therapy. Despite advances in therapy over the past few decades, the overall morbidity and mortality rates are still high, emphasizing the need for improved therapeutic choices to improve survival and quality of life further. Nano pharmaceuticals have demonstrated encouraging outcomes in in vivo trials using microscopic particles to enhance bioavailability and selectivity. The most successful clinical results to date have been achieved by liposomes, extracellular vesicles, and biomimetic nanoparticles; nevertheless, clinical trials are required to confirm their safety, efficacy, affordability, longterm impact, and success in patients from various demographics. Nano pharmaceuticals have the potential to change the paradigm of therapy for brain tumors, allowing better outcomes as primary and adjunctive therapy.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LMNB1/CDKN1A Signaling Regulates the Cell Cycle and Promotes Hepatocellular Carcinoma Progression.","authors":"Dute Gao, Huahu Guo, Zhaochen Liu, Liang Bao, Suxin Li, Yunchao Wang, Jiange Qiu, Binghua Jiang, Xiaowei Dang","doi":"10.2174/0115680096299107240427073527","DOIUrl":"10.2174/0115680096299107240427073527","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies in the world. Lamin B1 (LMNB1) is a key component of the nuclear skeleton structure. Recent studies have found that LMNB1 is overexpressed in tumor tissues and is associated with the prognosis of patients. However, the underlying mechanism remains unclear in HCC.</p><p><strong>Objective: </strong>This study aims to explore the clinical significance and molecular mechanisms of LMNB1 in HCC.</p><p><strong>Methods: </strong>The expression level of LMNB1 and its clinical values were analyzed with public databases, and the level of LMNB1 in HCC tissues and adjacent normal tissues was confirmed by qRT-PCR and IHC. Functional assays were conducted to explore the impact of LMNB1 knockdown on cell proliferation both in vivo and in vitro. Additionally, Genes and Genomes enrichment analysis, recovery analysis, and ChIP assays were employed to investigate its underlying molecular mechanisms. Finally, we carried out an analysis of the relationship between LMNB1 and immune cell infiltration in HCC.</p><p><strong>Results: </strong>LMNB1 was found to be overexpressed in HCC and correlated with the pathological stage and unfavorable prognosis. Functional assays demonstrated that LMNB1 promotes HCC proliferation both in vitro and in vivo. Further analysis revealed that LMNB1 promotes the progression of HCC by regulating CDKN1A expression. Furthermore, the infiltration of immune cells in HCC tissues suggests a potential correlation between immune infiltration cell markers and the expression of LMNB1.</p><p><strong>Conclusions: </strong>LMNB1 emerged as a promising therapeutic target and prognostic biomarker for HCC, with its expression showing a correlation with several immune infiltration cell markers.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Carbothioamide and Carboxamide Derivatives of 3-Phenoxybenzoic Acid as Potent VEGFR-2 Inhibitors: Synthesis, Molecular Docking, and Cytotoxicity Assessment.","authors":"Mohammad Hamza Heriz, Ammar A Razzak Mahmood, Lubna H Tahtamouni, Mai F AlSakhen, Sana I Kanaan, Khaled M Saleh, Salem R Yasin","doi":"10.2174/0115680096307334240429050730","DOIUrl":"https://doi.org/10.2174/0115680096307334240429050730","url":null,"abstract":"<p><strong>Introduction/background: </strong>Because of the well-established link between angiogenesis and tumor development, the use of antiangiogenic therapeutics, such as those targeting VEGFR-2, presents a promising approach to cancer treatment. In the current study, a set of five hydrazine-1-- carbothioamide (compounds 3a-e) and three hydrazine-1-carboxamide derivatives (compounds 4a-c) were successfully synthesized from 3-phenoxybenzoic acid. These compounds were specially created as antiproliferative agents with the goal of targeting cancer cells by inhibiting VEGFR-2 tyrosine kinase.</p><p><strong>Materials and methods: </strong>The new derivatives were synthesized by conventional organic methods, and their structure was versified by IR, 1HNMR, 13CNMR, and mass spectroscopy. In silico investigation was carried out to identify the compounds' target, molecular similarity, ADMET, and toxicity profile. The cytotoxic activity of the prepared compounds was evaluated in vitro against three human cancer cell lines (DLD1 colorectal adenocarcinoma, HeLa cervical cancer, and HepG2 hepatocellular carcinoma). The effects of the leading compound on cell cycle progression and apoptosis induction were investigated by flow cytometry, and the specific apoptotic pathway triggered by the treatment was evaluated by RT-PCR and immunoblotting. Finally, the inhibitory activities of the new compounds against VEGFR-2 was measured.</p><p><strong>Results: </strong>The designed derivatives exhibited comparable binding positions and interactions to the VEGFR-2 binding site to that of sorafenib (a standard VEGFR-2 tyrosine kinase inhibitor), as determined by molecular docking analysis. Compound 4b was the most cytotoxic compound, achieving the lowest IC50 against HeLa cells. Compound 4b, a strong representative of the synthesized series, induced cell cycle arrest at the G2/M phase, increased the proportion of necrotic and apoptotic HeLa cells, and activated caspase 3. The EC50 value of compound 4b against VEGFR-2 kinase activity was comparable to sorafenib's.</p><p><strong>Conclusion: </strong>Overall, the findings suggest that compound 4b has a promising future as a starting point for the development of new anticancer drugs.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140921705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Antitumor Efficacy of PEGylated Liposomes Loaded with Licorice Extract for Cancer Therapy","authors":"Zeinab Azizi Haghighat, Aliakbar Safekordi, Mehdi Ardjmand, Azim Akbarzadeh","doi":"10.2174/0115680096292153240416115744","DOIUrl":"https://doi.org/10.2174/0115680096292153240416115744","url":null,"abstract":"Background: Glycyrrhizic Acid (GA), a compound derived from licorice, has exhibited promising anticancer properties against several cancer types, including Prostate Cancer (PCa) and Gastric Cancer (GCa). Objective: This study has introduced a novel approach involving the encapsulation of GA and Licorice extract (Lic) into Polyethylene Glycol Liposomes (PEG-Lip) and assessed their efficacy against AGS (human gastric cancer) and PC-3 (human prostate cancer) cells, marking the first report of this endeavor. Methods: We synthesized GA-loaded PEG-Lip (GA PEG-Lip) and Lic-loaded PEG-Lip (Lic PEG-Lip) through the reverse-phase evaporation method. Results: Characterization of these liposomal formulations revealed their size, drug encapsulation, and loading efficiencies to be 110 ± 2.05 nm, 117 ± 1.24 nm; 61 ± 0.81%, 34 ± 0.47%; and 8 ± 0.41% and 4.6 ± 0.21%, respectively. Importantly, the process has retained the chemical structure of both GA and Lic. Furthermore, GA and Lic have been released from the PEG-Lip formulations in a controlled manner. In our experiments, both nanoformulations exhibited enhanced cytotoxic effects against AGS and PC-3 cells. Notably, GA PEG-Lip outperformed Lic PEG-Lip, reducing the viability of PC-3 and AGS cells by 12.5% and 15.9%, respectively. Conclusion: These results have been corroborated by apoptosis assays, which have demonstrated GA PEG-Lip and Lic PEG-Lip to induce stronger apoptotic effects compared to free GA and Lic on both PC-3 and AGS cells. This study has underscored the potential of encapsulating GA and Lic in PEG-Lip as a promising strategy to augment their anticancer efficacy against prostate and gastric cancers. conclusion: These results were corroborated by apoptosis assays, which demonstrated that GA PEG-Lip and Lic PEG-Lip induced stronger apoptotic effects compared to free GA and Lic on both PC-3 and AGS cells. This study underscores the potential of encapsulating GA and Lic in PEG-Lip as a promising strategy to augment their anticancer efficacy against prostate and gastric cancers. other: The research implications include: Advancement in cancer treatment, Overcoming the limitations of GA, innovation in drug delivery, contribution to nanomedicine","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140829000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low Expression MCEMP1 Promoting Lung Adenocarcinoma Progression by and its Clinical Value","authors":"Liqun Ling, Tianqi Hu, Chenkang Zhou, Shuhui Chen, Lunan Chou, Yuxin Chen, Zhaoting Hu, Kate Huang, Jie Chen, Yumin Wang, Junjun Wang","doi":"10.2174/0115680096292054240409070618","DOIUrl":"https://doi.org/10.2174/0115680096292054240409070618","url":null,"abstract":"Objective: We aimed to investigate the role of MCEMP1 in LUAD. Methods: MCEMP1 expression in LUAD was analyzed using The Cancer Genome Atlas (TCGA) data, and conducted univariate and multivariate Cox regression analyses to evaluate the prognostic significance of MCEMP1 expression in TCGA. Tumor Immune Estimation Resource (TIMER) was used for examining the correlation between MCEMP1 expression and immune cell infiltration in LUAD. Furthermore, proliferation, migration, invasion, and colony-forming ability were investigated using LUAD cell lines. Results: MCEMP1 had low expression in LUAD patient tissues and was correlated with lymph node metastasis, differentiation level, and tumor status. The Area under Curve (AUC) value of MCEMP1 for the Receiver Operating Characteristic (ROC) curve analysis was 0.984. The immune infiltration analysis revealed a correlation between MCEMP1 expression and the extent of macrophages and neutrophil infiltration in LUAD. Additionally, MCEMP1 has low expression in clinical samples, MCEMP1 overexpressed in LUAD cells substantially reduced cell growth, migration, and invasion of malignant cells. Conclusion: Low expression MCEMP1 promotes LUAD progression, which provides new insights and a potential biological target for future LUAD therapies.","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140809212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Smart Nanobiomaterials for Gene Delivery in Localized Cancer Therapy: An Overview from Emerging Materials and Devices to Clinical Applications.","authors":"Armin Shamaeizadeh, Anahita Beigi, S. M. Naghib, Maryam Tajabadi, M. Rahmanian, M. R. Mozafari","doi":"10.2174/0115680096288917240404060506","DOIUrl":"https://doi.org/10.2174/0115680096288917240404060506","url":null,"abstract":"Researchers in various fields continue to discover improved ways of local delivery of drugs to specific locations and try to increase the efficiency of these methods. Extensive research has been done on smart nano-biomaterials for drug delivery systems (DDS) in different dimensions. With the advancement of biomedical nanotechnology, conventional smart DDS with stimuli- responsive capability has been developed. Smart nano-biomaterials can respond to environmental changes caused by endogenous or exogenous elements: endogenous factors such as environmental pH, temperature gradient, enzymes, oxidation, and reduction potential. As well as exogenous factors, including light radiation, ultrasound, electric and magnetic fields. Currently, smart DDSs count as a major category in DDS and disease treatment. Currently, smart DDS are of great interest in drug delivery and treatment of diseases. With the improvements in gene and protein therapy, new methods have been presented to treat diseases without effective conventional treatment, especially cancer. Finally, the use of nanoparticles expanded due to the need for appropriate gene and protein delivery systems. This review discusses the advantages of protein and gene therapy, their challenges, and gene and protein delivery systems with nanoparticle-based delivery.","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140684446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The HGF/Met Receptor Mediates Cytotoxic Effect of Bacterial Cyclodipeptides in Human Cervical Cancer Cells","authors":"Laura Hernández-Padilla, Mayra X. Durán-Maldonado, Lorena Martínez-Alcantar, José S. Rodríguez-Zavala, Jesus Campos-Garcia","doi":"10.2174/0115680096285034240323035013","DOIUrl":"https://doi.org/10.2174/0115680096285034240323035013","url":null,"abstract":"Background: Human cervix adenocarcinoma (CC) caused by papillomavirus is the third most common cancer among female malignant tumors. Bioactive compounds such as cyclodipeptides (CDPs) possess cytotoxic effects in human cervical cancer HeLa cells mainly by blocking the PI3K/Akt/mTOR pathway and subsequently inducing gene expression by countless transcription regulators. However, the upstream elements of signaling pathways have not been well studied. Methods: To elucidate the cytotoxic and antiproliferative responses of the HeLa cell line to CDPs by a transcriptomic analysis previously carried out, we identified by immunochemical analyses, differential expression of genes related to the hepatocyte growth factor/mesenchymal-epithelial transition factor (HGF/MET) receptors. Furthermore, molecular docking was carried out to evaluate the interactions of CDPs with the EGF and MET substrate binding sites. Results: Immunochemical and molecular docking analyses suggest that the HGF/MET receptor participation in CDPs cytotoxic effect was independent of the protein expression levels. However, protein modulation of downstream Met-targets occurred due to the inhibition of phosphorylation of the HGF/MET receptor. Results suggest that the antiproliferative and cytotoxicity of CDPs in HeLa cells involve the HGF/MET receptor upstream of PI3K/Akt/mTOR pathway; assays with the human breast cancer MCF-7 and MDA-MB-231cell lines supported the finding. Conclusion: Data provide new insights into the molecular mechanisms involved in CDPs cytotoxicity and antiproliferative effects, suggesting that the signal transduction mechanism may be related to the inhibition of the phosphorylation of the EGF/MET receptor at the level of substrate binding site by an inhibition mechanism similar to that of Gefitinib and foretinib anti-neoplastic drugs.","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140608390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Detection, Precision Treatment, Recurrence Monitoring: Liquid Biopsy Transforms Colorectal Cancer Therapy","authors":"Harshvardhan Raval, Sankha Bhattacharya","doi":"10.2174/0115680096295070240318075023","DOIUrl":"https://doi.org/10.2174/0115680096295070240318075023","url":null,"abstract":": Colorectal cancer (CRC) is a significant global health concern. We need ways to detect it early and determine the best treatments. One promising method is liquid biopsy, which uses cancer cells and other components in the blood to help diagnose and treat the disease. Liquid biopsies focus on three key elements: circulating tumor DNA (ctDNA), circulating microRNA (miRNA), and circulating tumor cells (CTC). By analyzing these elements, we can identify CRC in its early stages, predict how well a treatment will work, and even spot signs of cancer returning. This study investigates the world of liquid biopsy, a rapidly growing field. We want to understand how it can help us better recognize the molecular aspects of cancer, improve and diagnostics, tailor treatments to individual patients, and keep track of the disease over the long-term. We explored specific components of liquid biopsy, like extracellular vesicles and cell-free DNA, and how they are used to detect CRC. This review sheds light on the current state of knowledge and the many ways a liquid biopsy can be used in treating colorectal cancer. It can transform patient care, disease management, and clinical outcomes by offering non-invasive cancer-targeting solutions.","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140564631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"L-lysine Increases the Anticancer Effect of Doxorubicin in Breast Cancer by Inducing ROS-Dependent Autophagy","authors":"Mozhgan Jahani, Reza Yarani, Davood Rezazadeh, Hadis Tahmasebi, Zohreh Hoseinkhani, Sara Kiani, Kamran Mansouri","doi":"10.2174/0115680096288665240315072646","DOIUrl":"https://doi.org/10.2174/0115680096288665240315072646","url":null,"abstract":"Background:: Doxorubicin (DOX) is a chemotherapy drug that is widely used in cancer therapy, especially in Triple-Negative Breast Cancer (TNBC) patients. Nevertheless, cytoprotective autophagy induction by DOX limits its cytotoxic effect and drug resistance induction in patients. Therefore, finding a new way is essential for increasing the effectiveness of this drug for cancer treatment. Objective:: This study aimed to investigate the effect of L-lysine on DOX cytotoxicity, probably through autophagy modulation in TNBC cell lines. Methods:: We used two TNBC cell lines, MDA-MB-231 and MDA-MB-468, with various levels of autophagy activity. Cell viability after treatment with L-lysine alone and in combination therapy was evaluated by MTT assay. Reactive Oxygen Species (ROS), nitric oxide (NO) concentration, and arginase activity were assessed using flow cytometric analysis, Griess reaction, and arginase activity assay kit, respectively. Real-time PCR and western blot analysis were used to evaluate the L-lysine effect on the autophagy-related genes and protein expression. Cell cycle profile and apoptotic assay were performed using flow cytometric analysis. Results:: The obtained data indicated that L-lysine in both concentrations of 24 and 32 mM increased the autophagy flux and enhanced the DOX cytotoxicity, especially in MDA-MB-231, which demonstrated higher autophagy activity than MDA-MB-468, by inducing ROS and NO production. Furthermore, L-lysine induced G2/M arrest autophagy cell death, while significant apoptotic changes were not observed. Conclusion:: These findings suggest that L-lysine can increase DOX cytotoxicity through autophagy modulation. Thus, L-lysine, in combination with DOX, may facilitate the development of novel adjunct therapy for cancer.","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140564405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}