Anti-cancer agents in medicinal chemistry最新文献

{"title":"Anti-lung Cancer Activity of Synthesized Substituted 1,4-Benzothiazines: An Insight from Molecular Docking and Experimental Studies.","authors":"Andleeb Amin, Zubaid-Ul- Khazir, Arfa Ji, Basharat Ahmad Bhat, Dar Murtaza, Aaqib A Hurrah, Imtiyaz A Bhat, Shaheena Parveen, Syed Nisar, Praveen Kumar Sharma","doi":"10.2174/0118715206276737231103114924","DOIUrl":"10.2174/0118715206276737231103114924","url":null,"abstract":"<p><strong>Background: </strong>Thiazine, a 6-membered distinctive heterocyclic motif with sulfur and nitrogen atoms, is one of the heterocyclic compounds that functions as a core scaffold in a number of medicinally significant molecules. Small thiazine-based compounds may operate simultaneously on numerous therapeutic targets and by employing a variety of methods to halt the development, proliferation, and vasculature of cancer cells. We have, herein, reported a series of substituted 1,4 benzothiazines as potential anticancer agents for the treatment of lung cancer.</p><p><strong>Methods: </strong>In order to synthesize 2,3-disubstituted-1,4 benzothiazines in good yield, a facile green approach for the oxidative cycloaddition of 2-amino benzenethiol and 1,3-dicarbonyls employing a catalytic amount of ceric ammonium nitrate has been devised. All the molecules have been characterized by spectral analysis and tested for anticancer activity against the A-549 lung cancer cell line using various functional assays. Further in silico screening of compound 3c against six crucial inflammatory molecular targets, such as Il1-α (PDB ID: 5UC6), Il1- β (PDB ID: 6Y8I), Il6 (PDB ID: 1P9M), vimentin (PDB ID: 3TRT), COX-2 (PDB ID: 5KIR), Il8 (PDB ID: 5D14), and TNF-α (PDB ID: 2AZ5), was done using AutoDock tool.</p><p><strong>Results: </strong>Among the synthesized compounds, propyl 3-methyl-3,4-dihydro-2H-benzo[b][1,4]thiazine-2- carboxylate (3c) was found to be most active based on cell viability assays using A-549 lung cancer cell line and was found to effectively downregulate various pro-inflammatory genes, like Il1-α, Il1-β, Il6, vimentin, COX-2, Il8, and TNF-α <i>in vitro</i>. The ability of the molecule to effectively suppress the proliferation and migration of lung cancer cells <i>in vitro</i> has been further demonstrated by the colony formation unit assay and wound healing assay. Molecular docking analysis showed the maximal binding affinity (- 7.54 kcal/mol) to be exhibited by compound 3c against IL8.</p><p><strong>Conclusion: </strong>A green unconventional route for the synthesis of 2,3-disubstituted-1,4 benzothiazines has been developed. All the molecules were screened for their activity against lung cancer and the data suggested that the presence of an additional unbranched alkyl group attached to the thiazine ring increased their activity. Also, <i>in vitro</i> and <i>in silico</i> modeling confirmed the anti-cancer efficiency of compound 3c, encouraging the exploration of such small molecules against cancer.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"358-371"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92152290","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":"Germacrone: A Multi-targeting Sesquiterpene with Promising Anti-cancer and Chronic Disease Applications.","authors":"Navin Kumar Tailor, Ajmer Singh Grewal, Geeta Deswal, Ashwani Kumar Dhingra","doi":"10.2174/0118715206312324240805075050","DOIUrl":"10.2174/0118715206312324240805075050","url":null,"abstract":"<p><strong>Background: </strong>Germacrone, a naturally occurring active compound found in essential oils extracted from medicinal plants within the Zingiberaceae family, has garnered attention for its potential therapeutic applications. Extensive research has highlighted its multi-targeting capabilities, positioning it as a promising treatment for various chronic diseases, including cancer, cardiovascular conditions, and neurodegenerative disorders like Alzheimer's disease.</p><p><strong>Objective: </strong>This review aims to provide a comprehensive overview of germacrone as a scaffold for developing multi-targeting drugs with therapeutic potential against a range of chronic disorders. The study delves into the molecular mechanisms that underlie the therapeutic effects of germacrone and explores its potential targets, including NF-κB, PI3K/AKT/mTOR, p53, JAK/STAT, caspase, apoptosis, and autophagy induction.</p><p><strong>Methods: </strong>A systematic review of literature databases was conducted to gather relevant studies on germacrone and its therapeutic applications. The molecular mechanisms and potential targets of germacrone were examined to elucidate its multi-targeting capabilities.</p><p><strong>Results: </strong>Germacrone exhibits significant potential in the management of chronic diseases, with demonstrated effects on various cellular pathways. The review highlights its impact on NF-κB, PI3K/AKT/mTOR, p53, JAK/STAT, caspase, apoptosis, and autophagy induction, showcasing its versatility in targeting multiple pathways associated with chronic conditions. Germacrone has emerged as a promising candidate for the treatment of diverse chronic diseases. The understanding of its multi-targeting capabilities, coupled with its natural origin, positions it as a valuable scaffold for developing therapeutics.</p><p><strong>Conclusion: </strong>The exploration of germacrone as a structural framework for multi-targeting drugs offers a potential avenue to enhance efficacy while minimizing potential side effects. Further research and clinical trials are warranted to validate the therapeutic potential of germacrone in diverse medical contexts.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"1396-1406"},"PeriodicalIF":2.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900774","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":"Cyclanoline Reverses Cisplatin Resistance in Bladder Cancer Cells by Inhibiting the JAK2/STAT3 Pathway.","authors":"Linjin Li, Chengpeng Li, Feilong Miao, Wu Chen, Xianghui Kong, Ruxian Ye, Feng Wang","doi":"10.2174/0118715206304668240729093158","DOIUrl":"10.2174/0118715206304668240729093158","url":null,"abstract":"<p><strong>Background: </strong>Cisplatin is a key therapeutic agent for bladder cancer, yet the emergence of cisplatin resistance presents a significant clinical challenge.</p><p><strong>Objective: </strong>This study aims to investigate the potential and mechanisms of cyclanoline (Cyc) in overcoming cisplatin resistance.</p><p><strong>Methods: </strong>Cisplatin-resistant T24 and BIU-87 cell models (T24/DR and BIU-87/DR) were established by increasing gradual concentration. Western Blot (WB) assessed the phosphorylation of STAT3, JAK2, and JAK3. T24/DR and BIU-87/DR cell lines were treated with selective STAT3 phosphorylation modulators, and cell viability was evaluated by CCK-8. Cells were subjected to cisplatin, Cyc, or their combination. Immunofluorescence (IHC) examined p-STAT3 expression. Protein and mRNA levels of apoptosis-related and cell cycle-related factors were measured. Changes in proliferation, invasion, migration, apoptosis, and cell cycle were monitored. <i>In vivo</i>, subcutaneous tumor transplantation models in nude mice were established, assessing tumor volume and weight. Changes in bladder cancer tissues were observed through HE staining, and the p-STAT3 was assessed via WB and IHC.</p><p><strong>Results: </strong>Cisplatin-resistant cell lines were successfully established, demonstrating increased phosphorylation of STAT3, JAK2, and JAK3. Cisplatin or Cyc treatment decreased p-STAT3, inhibited invasion and migration, and induced apoptosis and cell cycle arrest in the G0/G1 phase <i>in vitro</i>. <i>In vivo</i>, tumor growth was significantly suppressed, with extensive tumor cell death. IHC and WB consistently showed a substantial downregulation of STAT3 phosphorylation. These changes were more pronounced when cisplatin and Cyc were administered in combination.</p><p><strong>Conclusion: </strong>Cyc reverses cisplatin resistance <i>via</i> JAK/STAT3 inhibition in bladder cancer, offering a potential clinical strategy to enhance cisplatin efficacy in treating bladder cancer.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"1360-1370"},"PeriodicalIF":2.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141915962","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":"Effects of Arborvitae (<i>Thuja plicata</i>) Essential Oil on Cervical Cancer Cells: Insights into Molecular Mechanisms.","authors":"Ruben Piña-Cruz, Andrea Molina-Pineda, Marco Aguila-Estrada, María Martha Villaseñor-García, Georgina Hernández-Flores, Luis Felipe Jave-Suarez, Adriana Aguilar-Lemarroy","doi":"10.2174/0118715206308864240823095507","DOIUrl":"10.2174/0118715206308864240823095507","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to assess the effects of AEO in an <i>in vitro</i> model of cell lines derived from cervical cancer-namely, HeLa and SiHa-by screening for AEO's cytotoxic properties and examining its influence on the modulation of gene expression.</p><p><strong>Background: </strong>Cervical cancer stands as a prevalent global health concern, affecting millions of women worldwide. The current treatment modalities encompass surgery, radiation, and chemotherapy, but significant limitations and adverse effects constrain their effectiveness. Therefore, exploring novel treatments that offer enhanced efficacy and reduced side effects is imperative. Arborvitae essential oil, extracted from <i>Thuja Plicata</i>, has garnered attention for its antimicrobial, anti-inflammatory, immunomodulatory, and tissue-remodeling properties; however, its potential in treating cervical cancer remains uncharted.</p><p><strong>Objective: </strong>The objective of this study was to delve into the molecular mechanisms induced by arborvitae essential oil in order to learn about its anticancer effects on cervical cancer cell lines.</p><p><strong>Methods: </strong>The methods used in this study were assessments of cell viability using WST-1 and annexin V- propidium iodide, mRNA sequencing, and subsequent bioinformatics analysis.</p><p><strong>Results: </strong>The findings unveiled a dose-dependent cytotoxic effect of arborvitae essential oil on both HeLa and SiHa cell lines. Minor effects were observed only at very low doses in the HaCaT non-tumorigenic human keratinocyte cells. RNA-Seq bioinformatics analysis revealed the regulatory impact of arborvitae essential oil on genes enriched in the following pathways: proteasome, adherens junctions, nucleocytoplasmic transport, cell cycle, proteoglycans in cancer, protein processing in the endoplasmic reticulum, ribosome, spliceosome, mitophagy, cellular senescence, and viral carcinogenesis, among others, in both cell lines. It is worth noting that the ribosome and spliceosome KEGG pathways are the most significantly enriched pathways in HeLa and SiHa cells.</p><p><strong>Conclusion: </strong>Arborvitae essential oil shows potential as a cytotoxic and antiproliferative agent against cervical cancer cells, exerting its cytotoxic properties by regulating many KEGG pathways.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"1483-1500"},"PeriodicalIF":2.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124549","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 Role of Non-coding RNAs in Regulating Ferroptosis in Cancer: Mechanisms and Application Prospects.","authors":"Ming-Yuan Cao, Zhen-Dong Zhang, Xin-Rui Hou, Xiao-Ping Wang","doi":"10.2174/0118715206322163240710112404","DOIUrl":"10.2174/0118715206322163240710112404","url":null,"abstract":"<p><p>Cancer is the second leading cause of death globally. Despite some successes, conventional cancer treatments are insufficient to address the growing problem of drug resistance in tumors and to achieve efficient treatment outcomes. Therefore, there is an urgent need to explore new therapeutic options. Ferroptosis, a type of iron- and reactive oxygen species-dependent regulated cell death, has been closely associated with cancer development and progression. Non-coding RNAs (ncRNAs) are a class of RNAs that do not code for proteins, and studies have demonstrated their involvement in the regulation of ferroptosis in cancer. This review aims to explore the molecular regulatory mechanisms of ncRNAs involved in ferroptosis in cancer and to emphasize the feasibility of ferroptosis and ncRNAs as novel therapeutic strategies for cancer. We conducted a systematic and extensive literature review using PubMed, Google Scholar, Web of Science, and various other sources to identify relevant studies on ferroptosis, ncRNAs, and cancer. A deeper understanding of ferroptosis and ncRNAs could facilitate the development of new cancer treatment strategies.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"1182-1196"},"PeriodicalIF":2.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632378","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":"Preparation, Characterization, and Anticancer Activity Assessment of Chitosan/TPP Nanoparticles Loaded with <i>Echis carinatus</i> Venom.","authors":"Maral Mahboubi Kancha, Mohsen Mehrabi, Fatemeh Sadat Bitaraf, Hamid Vahedi, Morteza Alizadeh, Andreas Bernkop-Schnürch","doi":"10.2174/0118715206279731231129105221","DOIUrl":"10.2174/0118715206279731231129105221","url":null,"abstract":"<p><strong>Aims and background: </strong><i>Echis carinatus</i> venom is a toxic substance naturally produced by special glands in this snake species. Alongside various toxic properties, this venom has been used for its therapeutic effects, which are applicable in treating various cancers (liver, breast, <i>etc.</i>).</p><p><strong>Objective: </strong>Nanotechnology-based drug delivery systems are suitable for protecting <i>Echis carinatus</i> venom against destruction and unwanted absorption. They can manage its controlled transfer and absorption, significantly reducing side effects.</p><p><strong>Methods: </strong>In the present study, chitosan nanoparticles were prepared using the ionotropic gelation method with emulsion cross-linking. The venom's encapsulation efficiency, loading capacity, and release rate were calculated at certain time points. Moreover, the nanoparticles' optimal formulation and cytotoxic effects were determined using the MTT assay.</p><p><strong>Results: </strong>The optimized nanoparticle formulation increases cell death induction in various cancerous cell lines. Moreover, chitosan nanoparticles loaded with <i>Echis carinatus</i> venom had a significant rate of cytotoxicity against cancer cells.</p><p><strong>Conclusion: </strong>It is proposed that this formulation may act as a suitable candidate for more extensive assessments of cancer treatment using nanotechnology-based drug delivery systems.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"533-543"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139511527","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":"Synthesis and Molecular Dynamic Simulation of Novel Cationic and Non-cationic Pyrimidine Derivatives as Potential G-quadruplex-ligands.","authors":"Hoda Atapour-Mashhad, Mohammad Soukhtanloo, Shiva Golmohammadzadeh, Jamshidkhan Chamani, Mojgan Nejabat, Farzin Hadizadeh","doi":"10.2174/0118715206291797240523112439","DOIUrl":"10.2174/0118715206291797240523112439","url":null,"abstract":"<p><strong>Background: </strong>Drug resistance has been a problem in cancer chemotherapy, which often causes shortterm effectiveness. Further, the literature indicates that telomere G-quadruplex could be a promising anti-cancer target.</p><p><strong>Objective: </strong>We synthesized and characterized two new pyrimidine derivatives as ligands for G-quadruplex DNA.</p><p><strong>Methods: </strong>The interaction of novel non-cationic and cationic pyrimidine derivatives (3a, b) with G-quadruplex DNA (1k8p and 3qsc) was explored by circular dichroism (CD) and ultraviolet-visible spectroscopy and polyacrylamide gel electrophoresis (PAGE) methods. The antiproliferative activity of desired compounds was evaluated by the MTT assay. Apoptosis induction was assessed by Propidium iodide (P.I.) staining and flow cytometry. Computational molecular modeling (CMM) and molecular dynamics simulation (MD) were studied on the complexes of 1k8p and 3qsc with the compounds. The van der Waals, electrostatic, polar solvation, solventaccessible surface area (SASA), and binding energies were calculated and analyzed.</p><p><strong>Results: </strong>The experimental results confirmed that both compounds 3a and 3b interacted with 1k8p and 3qsc and exerted cytotoxic and proapoptotic effects on cancer cells. The number of hydrogen bonds and the RMSD values increased in the presence of the ligands, indicating stronger binding and suggesting increased structural dynamics. The electrostatic contribution to binding energy was higher for the cationic pyrimidine 3b, indicating more negative binding energies.</p><p><strong>Conclusion: </strong>Both experimental and MD results confirmed that 3b was more prone to form a complex with DNA G-quadruplex (1k8p and 3qsc), inhibit cell growth, and induce apoptosis, compared to the non-cationic pyrimidine 3a.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"1126-1141"},"PeriodicalIF":2.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141260405","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":"Molecular Actions of <i>Enicostemma hyssopifolium</i> Whole Plant Extract on HPV18-Infected Human Cervical Cancer (HeLa) Cells.","authors":"Komal Parameshwarappa Koralahalli, Sardar Hussain, David Wilson Devarajan, Siddikuzzaman, Berlin Grace Viswanathan Mariammal","doi":"10.2174/0118715206296375240703115848","DOIUrl":"10.2174/0118715206296375240703115848","url":null,"abstract":"<p><strong>Objective: </strong><i>Enicostemma hyssopifolium</i> (<i>E. hyssopifolium</i>) contains several bioactive compounds with anti-cancer activities. This study was performed to investigate the molecular effects of <i>E. hyssopifolium</i> on HPV18-containing HeLa cells.</p><p><strong>Methods: </strong>The methanol extract of <i>E. hyssopifolium</i> whole plant was tested for cytotoxicity by MTT assay. A lower and higher dose (80 and 160 μg/mL) to IC₅₀ were analyzed for colonization inhibition (Clonogenic assay), cell cycle arrest (FACS analysis), and induction of apoptosis (AO/EtBr staining fluorescent microscopy and FACS analysis) and DNA fragmentation (comet assay). The HPV 18 E6 gene expression in treated cells was analyzed using RT-PCR and qPCR.</p><p><strong>Results: </strong>A significant dose-dependent anti-proliferative activity (IC₅₀ - 108.25±2 μg/mL) and inhibition of colony formation cell line were observed using both treatments. Treatment with 80 μg/mL of extract was found to result in a higher percent of cell cycle arrest at G₀/G₁ and G₂M phases with more early apoptosis, while 160 μg/mL resulted in more cell cycle arrest at SUBG0 and S phases with late apoptosis for control. The comet assay also demonstrated a highly significant increase in DNA fragmentation after treatment with 160 μg/mL of extract (tail moments-19.536 ± 17.8), while 80 μg/mL of extract treatment showed non-significant tail moment (8.152 ± 13.0) compared to control (8.038 ± 12.0). The RT-PCR and qPCR results showed a significant reduction in the expression of the HPV18 E6 gene in HeLa cells treated with 160 μg/mL of extract, while 80 μg/mL did not show a significant reduction.</p><p><strong>Conclusion: </strong>The 160 μg/mL methanol extract of <i>E. hyssopifolium</i> demonstrated highly significant anti-cancer molecular effects in HeLa cells.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"1253-1263"},"PeriodicalIF":2.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562460","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":"A Novel Tryptanthrin Derivative D6 Induces Apoptosis and DNA Damage in Non-small-cell Lung Cancer Cells Through Regulating the EGFR Pathway.","authors":"Haitao Long, Guanglong Zhang, Yue Zhou, Liqing Qin, Danxue Zhu, Jiayi Chen, Bo Liu, Huayuan Tan, Danping Chen, Zhurui Li, Chengpeng Li, Zhenchao Wang","doi":"10.2174/0118715206303721240715042526","DOIUrl":"10.2174/0118715206303721240715042526","url":null,"abstract":"<p><strong>Background: </strong>Non-small-cell lung cancer is a prevalent malignancy associated with significant morbidity and mortality rates. Tryptanthrin and its derivatives have exhibited potent antitumor activity.</p><p><strong>Objective: </strong>This study aims to investigate the inhibitory effect of a novel synthesized tryptanthrin derivative D6 on proliferation and the possible mechanism of human non-small cell lung cancer cell lines (A549) <i>in vitro</i>.</p><p><strong>Methods: </strong>In this study, MTT assay, cell migration, colony formation assay, cell cycle analysis, cell apoptosis, JC- 1 staining assay, reactive oxygen species analysis, proteomics, western blotting, high content screening and absorption titrations analysis were performed.</p><p><strong>Results: </strong>We found that D6 inhibited both the proliferation and migration, induced cell cycle arrest in the G2/M phase, increased levels of ROS, decreased mitochondrial membrane potential, and promoted apoptosis in A549 cells. Further mechanistic studies found that D6 reduced EGFR expression in A549 cells and inhibited the EGFR pathway by decreasing phosphorylation levels of EGFR, Stat3, AKT and Erk1/2. Moreover, DNA damage induced by D6 involved an increase in p53/MDM2 ratio and concentration-dependent accumulation of micronuclei.</p><p><strong>Conclusion: </strong>D6 demonstrated significant antitumor activity against A549 cells by inhibiting the EGFR signaling pathway, inducing DNA damage, and subsequently leading to oxidative stress, apoptosis, and cell cycle arrest. Our findings suggest that D6 exhibits potential as an NSCLC drug, owing to its attributes such as antiproliferative activity and ability to induce apoptosis by attenuating the EGFR-mediated signaling pathway.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"1275-1287"},"PeriodicalIF":2.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733401","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":"Revolutionizing Cancer Treatment: Unleashing the Power of Combining Oncolytic Viruses with CAR-T Cells.","authors":"Lin Zhang, ShuXian Guo, ShuYing Chang, Guan Jiang","doi":"10.2174/0118715206308253240723055019","DOIUrl":"10.2174/0118715206308253240723055019","url":null,"abstract":"<p><p>Oncolytic Viruses (OVs) have emerged as a promising treatment option for cancer thanks to their significant research potential and encouraging results. These viruses exert a profound impact on the tumor microenvironment, making them effective against various types of cancer. In contrast, the efficacy of Chimeric antigen receptor (CAR)-T cell therapy in treating solid tumors is relatively low. The combination of OVs and CAR-T cell therapy, however, is a promising area of research. OVs play a crucial role in enhancing the tumor-suppressive microenvironment, which in turn enables CAR-T cells to function efficiently in the context of solid malignancies. This review aims to provide a comprehensive analysis of the benefits and drawbacks of OV therapy and CAR-T cell therapy, with a focus on the potential of combining these two treatment approaches.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"1407-1418"},"PeriodicalIF":2.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756704","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}