Anti-cancer agents in medicinal chemistry最新文献

{"title":"Schisanhenol Inhibits the Proliferation of Hepatocellular Carcinoma Cells by Targeting Programmed Cell Death-ligand 1 via the STAT3 Pathways.","authors":"Zhihong Zhang, Yiwen Zhong, Xu Han, Xueyang Hu, Yuhan Wang, Lei Huang, Siying Li, Ziqing Li, Chunmei Wang, He Li, Jinghui Sun, Wenyue Zhuang, Mengyang Wang, Jianguang Chen, Wei Liu, Chang Liu, Xin Guo, Siyu Yuan, Jiping Wu","doi":"10.2174/0118715206349131241121091834","DOIUrl":"https://doi.org/10.2174/0118715206349131241121091834","url":null,"abstract":"<p><strong>Background: </strong>Programmed cell death-ligand 1 (PD-L1) is overexpressed in tumor cells, which promotes tumor cell survival and cell proliferation and causes tumor cells to escape T-cell killing. Schisanhenol, a biphenyl cyclooctene lignin-like compound, was extracted and isolated from the plant named Schisandra rubriflora (Franch.).</p><p><strong>Purpose: </strong>In this work, we studied the anticancer potential of schisanhenol and explored whether schisanhenol mediated its effect by inhibiting the expression of PD-L1 in vitro and in vivo.</p><p><strong>Materials and methods: </strong>In vitro, we performed western blot, immunofluorescence, immunoprecipitation, and colony formation assays to study the proteins, genes, and pathways related to the anti-tumour activity of schisanhenol. In vivo, we explored the antitumor activity of schisanhenol through orthotopic liver transplantation and subcutaneous transplantation tumor models of hepatocellular carcinoma (HCC) cells.</p><p><strong>Results: </strong>We found that schisanhenol decreased the viability of HCC cells. It inhibited the expression of programmed cell death ligand-1 (PD-L1), which plays a pivotal role in tumorigenesis. Subsequently, schisanhenol suppressed the expression of PD-L1 by decreasing the activation of STAT3. Furthermore, we found that schisanhenol inhibited the activation of STAT3 via JAK/STAT3 (T705), Src/STAT3 (T705), and PI3K/AKT/mTOR/STAT3 (S727) pathways. Colony formation tests showed that schisanhenol suppressed cell proliferation by inhibiting PD-L1. Schisanhenol also enhanced cytotoxic T lymphocytes (CTL) activity and regained their ability to kill tumour cells in co-culture. Finally, in vivo observation confirmed the antitumor activity of schisanhenol.</p><p><strong>Conclusion: </strong>Schisanhenol inhibits the proliferation of HCC cells by targeting PD-L1 via the STAT3 pathways. These findings prove that schisanhenol is a valuable candidate for HCC therapeutics and reveal previously unknown characteristics of schisanhenol.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982533","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":"Synergistic Anti-tumorigenic Effects of Cabazitaxel and Usnic Acid Combination on Metastatic Castration-Resistant Prostate Cancer Cells.","authors":"Ceyda Colakoglu Bergel, Isil Ezgi Eryilmaz, Ebrucan Bulut, Rumeysa Fatma Balaban, Unal Egeli, Gulsah Cecener","doi":"10.2174/0118715206336754241015062614","DOIUrl":"https://doi.org/10.2174/0118715206336754241015062614","url":null,"abstract":"<p><strong>Background: </strong>Prostate cancer (PC) affects millions of men, causing high mortality rates. Despite the treatment approaches, the options for metastatic castration-resistant prostate cancer (mCRPC), a lethal form of advanced PC, are still limited. Cabazitaxel (Cbx) is the last taxane-derived chemotherapeutic approved for Docetaxel- resistant mCRPC patients. However, its effects are limited due to the activation of several pathways. Therefore, new approaches are needed to increase the efficacy of Cbx. Usnic acid (UA) is a natural product with wellknown anti-tumorigenic and synergistic effects with various chemotherapeutics. Although the cytotoxicity of UA and Cbx has been evaluated on mCRPC cells, the anti-tumorigenic effect of UA combination with any taxane has not been investigated yet. Thus, we aimed to evaluate the possible synergistic effect of Cbx+UA in mCRPC cells.</p><p><strong>Methods: </strong>Cell viability and apoptosis were analyzed using WST-1 and Annexin-V. Morphological changes were visualized by fluorescent staining. Finally, cell cycle, mitochondrial health, and ROS levels were determined.</p><p><strong>Results: </strong>Based on WST-1 results, 25 μM UA exhibited significant additive and synergistic effects with the use of Cbx. Annexin V and cell cycle results showed that UA significantly enhanced the Cbx efficacy at increasing doses compared to using only Cbx (**p<0.01). Moreover, combined treatment significantly increased ROS levels and mitochondrial membrane depolarization compared with Cbx alone (**p<0.01).</p><p><strong>Conclusions: </strong>Thus, the results suggest that UA increased the anti-tumorigenic effects of Cbx on mCRPC cells by increasing apoptosis, causing an increase in intracellular ROS and disrupting mitochondrial health. Consequently, combining UA and Cbx offers a new combined therapeutic strategy for mCRPC treatment.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982535","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":"Advances in VEGFR Inhibitors: A Comprehensive Review of Novel Anticancer Agents.","authors":"Sumeet Jha, Sneha Gupta, Supriya Rani, Pinky Arora, Neeraj Choudhary, Shubham Kumar","doi":"10.2174/0118715206356712241202112641","DOIUrl":"https://doi.org/10.2174/0118715206356712241202112641","url":null,"abstract":"<p><p>Cancer, characterized by aberrant cell growth, presents a formidable health challenge, impacting millions of individuals worldwide each year. Among the myriad mechanisms facilitating tumor progression, Vascular Endothelial Growth Factor receptors (VEGFR) play a pivotal role in driving angiogenesis the process by which tumors develop their own blood supply. This vascularization not only supports tumor nourishment and growth but also facilitates metastasis, enabling cancer to spread to distant sites. VEGFR inhibitors offer a strategic approach to disrupt the VEGF-VEGFR binding pathway, thereby impeding angiogenesis, metastasis, and the proliferation of cancer cells. This review elucidates the latest advancements in medicinal chemistry pertaining to VEGFR inhibitors, showcasing a variety of chemical moieties and assessing their efficacy across different cancer cell lines. The novel compounds highlighted in this review exhibit significant promise for anticancer evaluation through targeted VEGFR kinase inhibition. A robust body of in vivo, in vitro, and ex vivo studies supports these findings, demonstrating the antitumor effects of these compounds. Computational analyses further enhance our understanding by predicting compound binding affinities, pharmacokinetics, and overall drug-likeness. Despite the significant progress made in developing effective VEGFR inhibitors, challenges remain in refining these agents for optimal cancer treatment. This review not only summarizes the advancements achieved in VEGFR inhibitor development but also emphasizes the ongoing hurdles that must be addressed to enhance the efficacy of cancer therapies.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982527","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":"Royal Jelly's Strong Selective Cytotoxicity Against Lung Malignant Cells and Macromolecular Alterations in Cells Observed by FTIR Spectroscopy.","authors":"Ferhunde Aysin","doi":"10.2174/0118715206355400241112084611","DOIUrl":"https://doi.org/10.2174/0118715206355400241112084611","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction/objective: &lt;/strong&gt;Several nutraceuticals, food, and cosmetic products can be developed using royal jelly. It is known for its potential health benefits, including its ability to boost the immune system and reduce inflammation. It is rich in vitamins, minerals, and antioxidants, which can improve general health. Royal jelly (RJ) is also being studied as a potential therapeutic agent for cancer and other chronic diseases. It is effective in reducing tumor growth and stimulating immunity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this study, we investigated the effects of royal jelly on cancerous A549 cells and healthy MRC-5 cells at various doses ranging from 1.25 to 10 mg/ml. Royal jelly's anti-proliferative effect was evaluated by MTT and SRB assay for 48 h. The induction of necrosis and apoptosis was assessed by flow cytometry as well. The relative amounts of major molecules in Royal jelly were determined by FTIR spectroscopy to identify key functional groups and molecular structures. In addition, this technique was used for the first time to detect changes in the macromolecular composition of lung cells treated with royal jelly. Thus, it provided insights into the relative abundance of proteins, lipids, and carbohydrates, which could correlate with their bioactive properties.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The antiproliferative effect of Royal jelly was found to be selective on A549 cells in a dose-dependent manner with an IC50 of 9.26 mg/mL, with no cytotoxic effects on normal MRC-5 cells. Moreover, Royal jelly induced predominantly necrotic cell death in A549 cells, %39.10 at 4 mg/ml and %57.88 at 10 mg/ml concentrations. However, the necrosis rate in MRC-5 cells was quite low, at 9.16% and 20.44% at the same doses. Royal jelly showed dose-dependent selective cytotoxicity toward A549 cells, whereas it exhibited no apparent cytotoxicity in MRC-5 cells. In order to identify the biomolecular changes induced by royal jelly, we used two unsupervised chemometric pattern recognition algorithms (PCA and HCA) on the preprocessed sample FTIR spectra to determine the effects of royal jelly on cell biochemistry. According to PCA and HCA results, RJ treatments especially affected biomolecules in A549 cells. The total spectral band variances in the PCA loading spectra were calculated for understanding biomolecular alterations. These plots revealed profound changes in the lipid, protein, and nucleic acid content of RJ-applied lung cells, primarily identifying RJ and H2O2 treated groups for A549 cells.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Ultimately, the selective cytotoxicity of royal jelly toward A549 cancerous cells suggests that royal jelly may be a promising therapeutic agent for identifying innovative lung cancer treatment strategies. Additionally, understanding the molecular alterations induced by royal jelly could guide the development of novel cancer treatments that exploit its bioactive properties. This could lead to more effectiv","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977224","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":"Origanum syriacum Induces Apoptosis in Lung Cancer Cells by Altering the Ratio of Bax/Bcl2.","authors":"Önder Yumrutaş, Pınar Yumrutaş, Mustafa Pehlivan, Murat Korkmaz, Demet Kahraman","doi":"10.2174/0118715206333509241112060647","DOIUrl":"https://doi.org/10.2174/0118715206333509241112060647","url":null,"abstract":"<p><strong>Background: </strong>The lung cancer is the leading cause of death worldwide. Although methods such as surgery, chemotherapy, radiotherapy, and immunotherapy are used for treatment, these treatments are sometimes inadequate. In addition, the number of chemotherapeutic agents used is very limited, and it is very important to use new natural agents that can increase the effect of these methods used in treatment.</p><p><strong>Objective: </strong>The present study was designed to determine the suppression of proliferation and induction of apoptosis activities and phenolic content of Origanum syriacum methanol extract (OsME) on lung cancer cells (A549).</p><p><strong>Methods: </strong>For this purpose, the cell viability of A549 cells exposed to OsME was first determined. The morphological changes of the cell were observed by an inverted phase contrast microscope. Moreover, the percentage of apoptotic and necrotic cells was determined by FACS with AnnexinV/Propodium iodide staining. Additionally, proapoptotic Bax and antiapoptotic Bcl-2 mRNA levels were determined by Real-time PCR. Phenolic compounds of OsME were detected by LC-MS-MS.</p><p><strong>Results: </strong>It was observed that the viability and proliferation of lung cancer cells decreased after the treatment of different concentrations of OsME. At a concentration of 200 mg/ml of OsME, most of the cell membrane structures were observed to disintegrate. Meanwhile, a 25 μg/ml concentration of OsME increased the Bax expression and percentage of late apoptotic cells. Vanillic acid and luteolin were identified as the main phenolic compounds of OsME.</p><p><strong>Conclusion: </strong>OsME exhibited antiproliferation activity on A549 cells and induced apoptosis at low doses.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977212","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":"N-Degron PROTACs as a Potential Therapeutic Approach for Chronic Myeloid Leukemia.","authors":"Grace Hohman, Mohamed A Eldeeb","doi":"10.2174/0118715206367166241230111659","DOIUrl":"https://doi.org/10.2174/0118715206367166241230111659","url":null,"abstract":"<p><p>Many oncoproteins are important therapeutic targets because of their critical role in inducing rapid cell proliferation, which represents one of the salient hallmarks of cancer. Chronic Myeloid Leukemia (CML) is a cancer of hematopoietic stem cells that is caused by the oncogene BCR-ABL1. BCR-ABL1 encodes a constitutively active tyrosine kinase protein that leads to the uncontrolled proliferation of myeloid cells, which is a hallmark of CML. A current therapeutic approach for the treatment of CML, Tyrosine Kinase Inhibitors (TKIs), effectively inactivates BCR-ABL1 kinase activity; however, drug resistance to TKIs limits the long-term potential for this treatment. Proteolysis Targeting Chimera (PROTAC) has emerged as a promising pharmacological approach for degrading, rather than inhibiting, targeted proteins by harnessing the ubiquitin-proteosome system. This process involves tagging a Protein of Interest (POI) with ubiquitin by the E3 ubiquitin ligases, which subsequently target the protein for proteasomal degradation. The N-end rule or the N-degron concept describes the correlation between the metabolic stability of a protein and the biochemical identity of its N-terminal amino acid. A recent work unveiled that N-degron PROTACs could offer a potential treatment for CML by targeting and degrading BCR-ABL1 proteins. Herein, we present the molecular and biochemical implications for targeting chronic myeloid leukemia.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942900","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":"Observation on the Therapeutic Efficacy of Camrelizumab Combined with Chemotherapy in Non-small Cell Lung Cancer and the Cutaneous Immune-related Adverse Events: A Retrospective Study.","authors":"Hongmei Wang, Jiali Xia, Aoyang Yu, Menghan Cao, Yang Zhao, Xiaobing Qin, Wenlou Liu, Zhengxiang Han, Guan Jiang","doi":"10.2174/0118715206350978241105080452","DOIUrl":"https://doi.org/10.2174/0118715206350978241105080452","url":null,"abstract":"<p><strong>Introduction: </strong>Immunotherapy targeting PD-1/PD-L1 shows significant benefits in lung cancer. Cutaneous immune-related adverse events (irAEs) are frequent, early-developing side effects of ICIs, and their potential role as prognostic markers in non-small cell lung cancer (NSCLC) therapy requires further exploration.</p><p><strong>Methods: </strong>Data of patients with NSCLC treated with camrelizumab Combined with chemotherapy were collected at Xuzhou Medical University from 2019 to 2023. Cutaneous irAEs were monitored using CTCAE v5.0, and therapeutic efficacy was assessed using RECIST 1.1 criteria for ORR and PFS. Multivariable Cox regression analysis identified independent predictors of PFS, and a nomogram was constructed to predict survival outcomes.</p><p><strong>Results: </strong>Data from 151 patients were analyzed. Significant differences in the objective response rate (ORR, P = 0.016) and progression-free survival (PFS, P < 0.0001) were detected between NSCLC patients, either with cirAEs or not. Besides, PFS was significantly different in NSCLC patients who were subgrouped by the time of first cutaneous irAEs occurrence (P = 0.011), duration of cutaneous irAEs (P = 0.002), grade of cutaneous irAEs (P = 0.002), the number of cutaneous irAEs(P = 0.021). The multivariable analysis also revealed that cirAEs were positively associated with survival outcomes (HR: 0.316, 95% CI, 0.193- 0.519, P＜0.001) for PFS. The nomogram was formulated based on the results of multivariate analysis and validated using an internal bootstrap resampling approach, which showed that the nomogram exhibited a sufficient level of discrimination according to the C-index 0.80 (95% CI, 0.748-0.850).</p><p><strong>Conclusion: </strong>The presence of cirAEs in NSCLC patients treated with camrelizumab combined with chemotherapy is indicative of better treatment efficacy and prognosis. This study supports the utility of cirAEs as biomarkers for predicting the validity of immunotherapy in NSCLC. It proposes a novel, multi-parameter prognostic model to assess patient outcomes more accurately.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942907","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":"Design and Evaluation of 5-Oxo-1,2,4-triazole-3-carboxamide Compounds as Promising Anticancer Agents: Synthesis, Characterization, In vitro Cytotoxicity and Molecular Docking Studies.","authors":"Rajitha Balavanthapu, Girija Sastry Vedula","doi":"10.2174/0118715206315373241014101856","DOIUrl":"https://doi.org/10.2174/0118715206315373241014101856","url":null,"abstract":"<p><strong>Background: </strong>Cancer presents a significant global health challenge, necessitating effective treatment strategies. While chemotherapy is widely employed, its non-specific nature can induce adverse effects on normal cells, prompting the exploration of targeted therapies. The 1,2,4-triazole scaffold has emerged as a promising element in anticancer drug development due to its structural diversity and potential to target cancer cells.</p><p><strong>Objective: </strong>This study aims to synthesize and evaluate novel derivatives derived from the 1,2,4-triazole scaffold for their potential as anticancer agents. Molecular docking techniques are employed to investigate the interactions between the designed derivatives and specific cancer-related targets, providing insights into potential underlying mechanisms.</p><p><strong>Methods: </strong>The synthesis involves a three-step process to produce 5-oxo-1,2,4-triazole-3-carboxamide derivatives. Various analytical techniques, including NMR and HRMS, validate the successful synthesis. Molecular docking studies utilize X-ray crystal structures of EGFR and CDK-4 obtained from the Protein Data Bank, employing the Schrödinger suite for ligand preparation and Glide's extra-precision docking modes for scoring.</p><p><strong>Results: </strong>The synthesis yields compounds with moderate to good yields, supported by detailed characterization. Molecular docking scores for the derivatives against EGFR and CDK-4 revealed diverse affinities influenced by distinct substituents. Compounds with hydroxyl, and halogen, substitutions exhibited notable binding affinities, while alkyl and amino substitutions showed varying effects. The 1,2,4-triazole derivatives demonstrated potential for targeted cancer therapy.</p><p><strong>Conclusion: </strong>The study highlights the successful synthesis of 5-oxo-1,2,4-triazole-3-carboxamides and their diverse interactions with cancer-related targets. The findings emphasized the potential of these derivatives as candidates for further development as anticancer agents, offering insights into structure-activity relationships. The 1,2,4-triazole scaffold stands out as a promising platform for advancing cancer treatment with enhanced precision and efficacy.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942894","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":"Heavy Metals Alter the Anti-cancer Potency of Medicinal Plants.","authors":"Amber Rizwan, Aatiquah Aqeel, Aisha Idris, Humaira Farooqi","doi":"10.2174/0118715206341220241120132600","DOIUrl":"https://doi.org/10.2174/0118715206341220241120132600","url":null,"abstract":"<p><p>This review investigates the outcome of heavy metal contamination on the anti-cancer properties of medicinal plants. Heavy metal pollution is a significant environmental concern globally, often found in soil and water due to industrial activities. Therapeutic plants are recognized because of their therapeutic attributes and their ability to absorbing these contaminants. This study examines how heavy metal exposure modifies the chemical composition and efficacy of medicinal plants against cancer cells. Through a comprehensive review of existing literature and experimental analysis, we explore the mechanisms by which heavy metals interact with bioactive compounds in medicinal plants, affecting their anti-cancer potency. Findings reveal intricate interactions among heavy metals and phytochemicals, leading to variations in cytotoxicity against cancer cells. Comprehending these interactions is crucial for optimizing the utilization of medicinal plants in cancer treatment and for developing approaches to alleviate the impacts of heavy metal contamination on their therapeutic potential. The urgency of this issue cannot be overstated, as it directly impacts our ability to effectively treat cancer and preserve our environment.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942899","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":"Anti-metastasis Effects and Mechanism of Action of Curcumin Analog (2E,6E)-2,6-bis(2,3-dimethoxybenzylidene) Cyclohexanone (DMCH) on the SW620 Colorectal Cancer Cell Line.","authors":"Nurul Fattin Che Rahim, Yazmin Hussin, Muhammad Nazirul Mubin Aziz, Mas Jaffri Masarudin, Shafinaz Abd Gani, Muhammad Nadeem Akhtar, Nik Mohd Afizan Nik Abd Rahman, Noorjahan Banu Alitheen","doi":"10.2174/0118715206336788241029050155","DOIUrl":"https://doi.org/10.2174/0118715206336788241029050155","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is the second-leading cause of cancer-related deaths. Curcumin has been reported to have suppressive effects in CRC and to address the physiological limitations of curcumin, a chemically synthesized curcuminoid analog, known as (2E,6E)-2,6-Bis (2,3-Dimethoxy benzylidine) cyclohexanone (DMCH), was developed and the anti-metastatic and anti-angiogenic properties of DMCH in colorectal cell line, SW620 were examined.</p><p><strong>Methods: </strong>The anti-metastatic effects of DMCH were examined in the SW620 cell line by scratch assay, migration, and invasion assay, while for anti-angiogenesis properties of the cells, the mouse aortic ring assay and Human Umbilical Vein Endothelial Cells (HUVEC) assay were conducted. The mechanism of action was determined by microarray-based gene expression and protein analyses.</p><p><strong>Results: </strong>The wound healing assay demonstrated that wound closure was decreased from 63.63 ± 1.44% at IC25 treatment to 4.54 ± 0.62% at IC50 treatment. Significant (p<0.05) reductions in the percentage of migrated and invaded cells were also observed in SW620, with values of 36.39 ± 3.86% and 44.81 ± 3.54%, respectively. Mouse aortic ring assays demonstrated a significant reduction in the formation of tubes and microvessels. Microarray and protein profiler results revealed that DMCH treatment has modulated several metastases, angiogenesisrelated transcripts, and proteins like Epidermal Growth Factor Receptor (EGFR), TIMP-1 (TIMP Metallopeptidase Inhibitor 1) and Vascular Endothelial Growth Factor (VEGF).</p><p><strong>Conclusion: </strong>DMCH could be a potential anti-cancer agent due to its capability to impede metastasis and angiogenesis activities of the SW620 colorectal cancer cell line in vitro via regulating genes and protein in metastases and angiogenesis-related signalling pathways.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942891","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}