Anti-cancer agents in medicinal chemistry最新文献

{"title":"Potentials of N-Acyl hydrazones Against Colorectal Cancer: A Mini Review.","authors":"Darna Mounika, Sai Satya Sri Pulla, Swapnil Anil Sule, Vidya Jyothi Alli, Surender Singh Jadav","doi":"10.2174/0118715206356253241223040825","DOIUrl":"https://doi.org/10.2174/0118715206356253241223040825","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is a malignant gastrointestinal tract disorder with high occurrence and mortality index and showing an upsurge. Standard therapies for treating CRC are surgery and chemotherapy. Despite great effort in developing effective treatments, the progress is limited due to its relapse and recurrence. Prognosis of metastatic CRC is always complicated. This condition can be evaded by a novel approach i.e., targeted therapy which increases the survival rate in CRC patients by blocking important pathways and acting on immune checkpoints. Drugs with N-acyl hydrazones (NAH) are currently being employed treatment of infectious diseases and disorders. NAH in combination with diverse heterocycles, natural product isolates are identified as interesting CRC inhibitors under-explored. This review provides an overview of the existing CRC targeted compounds having acyl hydrazones, hydrazine, hydrazides moieties, and their underlying mechanisms towards different CRC cell lines, together with a discussion of their limitations and future trends.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031851","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":"Unveiling the Potential of S4 on Non-small Cell Lung Cancer Cells: Impact on Proliferation, Apoptosis, Senescence, and Metabolome Profile.","authors":"Turan Demircan, Mervenur Yavuz, Aydın Bölük","doi":"10.2174/0118715206350735241224073200","DOIUrl":"https://doi.org/10.2174/0118715206350735241224073200","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer is a highly aggressive tumor with limited therapeutic options. The misregulation of Androgen Receptor (AR) signaling has been observed in lung cancer. Therefore, inhibiting AR signaling is a promising strategy for treating lung cancer.</p><p><strong>Objective: </strong>Selective Androgen Receptor Modulators (SARMs) are small molecule drugs with a high affinity for the AR. S4, a member of SARMs was potentially positioned as a promising therapeutic agent in A549 lung cancer cells owing to its high bioavailability, lesser side effects, and novelty in cancer.</p><p><strong>Methods: </strong>We employed several techniques to investigate the potential anti-carcinogenic effect of S4 on A549 cells at cellular level. The cytotoxicity of S4 was investigated thorough MTT, and the IC50 value was identified as 0.22 mM. Then, the anchorage-dependent and -independent colonization of cells were assessed by colony formation and soft agar assays, respectively. Additionally, migration capacity, apoptosis, proliferation, senescene, cell-cycle progression of cells was examined thoroughly. In addition, gene expression profile and metabolome signature were explored via qRT-PCR and metabolomics, respectively to provide molecular links for S4 mode of action.</p><p><strong>Results: </strong>Our findings demonstrate that S4 inhibited growth, migration, and proliferation while inducing apoptosis. S4 significantly upregulated the BAX, CDKN1A, PUMA, and GADD45A genes while downregulating MKI67, BIRC5, and PCNA expression. S4 treatment drastically altered the metabolome signature, and enrichment of cancer related pathways by altered metabolites was noteworthy.</p><p><strong>Conclusion: </strong>We report the first study evaluating the potential anti-carcinogenic effects of S4 on lung cancer invitro which would bridge the gap on the utility of SARMs as inhibitors of lung cancer. Our results suggest that S4 could be considered as a promising drug candidate to test further for lung cancer treatment.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021761","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":"Chlorogenic Acid Ameliorates CCl4-induced Liver Fibrosis by Modulating the PI3K/AKT/mTOR Autophagy Pathway.","authors":"Amr Negm, Amira A El-Neanaey, Abada El Sayed Khadr, Maher Abd El Naby Kamel, Abd El-Hamid Abdo Ismail, Ibrahim El Tantawy El Sayed, Wael Sobhy Darwish, Mabrouk Attia Abd Eldaim, Raghda Sobhy Okaz, Mohamed Hamdy Bahr, Nihal Almuraikhi, Nermine Beshara, Tamer M Shawky, Ezat A Mersal","doi":"10.2174/0118715206357043250116063202","DOIUrl":"https://doi.org/10.2174/0118715206357043250116063202","url":null,"abstract":"<p><strong>Background: </strong>Liver fibrosis represents a serious risk to global health by impairing quality of life and elevating the chances of hepatocellular carcinoma, while the intricate role of autophagy can either alleviate or worsen fibrosis depending on its functioning.</p><p><strong>Objective: </strong>Herein, we aimed to investigate the therapeutic effect of chlorogenic acid in CCl4-induced hepatic fibrosis and explore the autophagy pathway as the possible molecular target of chlorogenic acid.</p><p><strong>Methods: </strong>Rats were injected with carbon tetrachloride (1ml/kg) to induce liver fibrosis for 10 weeks. In the current study, the liver fibrosis rats were treated daily with chlorogenic acid (20, 40, and 60 mg/kg) for 30 days. Liver function tests, renal function tests, lipid peroxidation, antioxidant enzyme, anti-inflammatory NF-κB level, and autophagy pathway parameters (PI3K, AKT, mTOR, LC3, and Beclin-1) were assessed.</p><p><strong>Results: </strong>CCl4 elevated serum AST and ALT activity, and hepatic malondialdehyde, PI3K, AKT, and mTOR expressions. It decreased LC3, Beclin-1 expression, and hepatic glutathione level. The results indicated that chlorogenic acid treatment ameliorated the hepatic functions. It declined serum AST and ALT activities, improved hepatic GSH concentration, decreased lipid peroxidation, and downregulated PI3K, AKT, and mTOR protein expressions in hepatic tissue. Moreover, chlorogenic acid increased the hepatic expression of LC3 and Beclin-1. It also significantly decreased NF-kB expression.</p><p><strong>Conclusion: </strong>Chlorogenic acid showed promise in reducing liver damage in rats caused by CCl4 by influencing the autophagy process and adjusting levels of antioxidant and inflammatory markers.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021748","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 Citrus-derived Diosmetin on Melanoma: Induction of Apoptosis and Autophagy Mediated by PI3K/Akt/mTOR Pathway Inhibition.","authors":"Jie Li, Mingyuan Xu, Nanhui Wu, Fei Wu, Jiashe Chen, Xiaoxiang Xu, Fei Tan, Yeqiang Liu","doi":"10.2174/0118715206360266250115065234","DOIUrl":"https://doi.org/10.2174/0118715206360266250115065234","url":null,"abstract":"<p><strong>Background: </strong>Diosmetin (DIOS) is a naturally abundant flavonoid and possesses various biological activities that hold promise as an anti-cancer agent. However, the anti-cancer activities and underlying mechanism of DIOS on cutaneous melanoma remain unclear.</p><p><strong>Objective: </strong>This study seeks to explore the anti-tumor effect and mechanism of DIOS in cutaneous melanoma.</p><p><strong>Methods: </strong>Here, a variety of in vitro and in vivo experiments, combined with RNA sequencing (RNA-seq), were employed to ascertain the potential anti-cutaneous melanoma capacity and mechanism of DIOS.</p><p><strong>Results: </strong>The results demonstrated that DIOS considerably impeded cell proliferation and triggered cell apoptosis in a dose- and time-dependent manner. Concurrently, DIOS markedly elevated the expression of pro-apoptotic proteins (Cleaved caspase-3, Bax, Cleaved PARP, and Cleaved caspase-9) and downregulated the expression of Bcl-2. Additionally, DIOS markedly upregulated the protein expressions of LC3B-II and Atg5, while downregulating p62 protein expression. Notably, pre-treatment with an autophagy inhibitor significantly inhibited DIOSinduced cell apoptosis and autophagy. Mechanistically, DIOS was identified to repress the PI3K/Akt/mTOR signaling pathway by western blot analyses and RNA-seq. Finally, in vivo experiments using a syngeneic mouse model confirmed the anti-tumor effect of DIOS, which exhibited high levels of apoptosis and autophagy.</p><p><strong>Conclusion: </strong>These findings propose that DIOS acts as a potential melanoma therapy that exerts its anti-tumor effects by triggering apoptosis and autophagy via inhibition of the PI3K/Akt/mTOR pathway.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021816","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":"Optimized Rutin-incorporating PEGylated Nanoliposomes as a Model with Remarkable Selectivity Against PANC1 and MCF7 Cell Lines","authors":"Ali Al-Samydai, Moath Al Qaraleh, Lidia K Al-Halaseh, Maha N Abu Hajleh, Simone Carradori, Maryam Abdulmaged, Rand Kareem, Hasanain Alzaidi, Mohamad Ak Mousa, Yusuf Al-Hiari, Hamdi Nsairat, Walhan Alshaer","doi":"10.2174/0118715206231749241209073759","DOIUrl":"10.2174/0118715206231749241209073759","url":null,"abstract":"<p><strong>Background: </strong>This study aims to enhance the delivery of polyphenols using nanotechnology.</p><p><strong>Objective: </strong>To develop and evaluate liposomal formulations for improved delivery and stability of polyphenols, specifically focusing on Rutin.</p><p><strong>Methods: </strong>Liposomal formulations were meticulously prepared via the Thin-Film Hydration method. Comprehensive physical characterization was conducted, including stability assessments using Dynamic Light Scattering (DLS) and Thermogravimetric Analysis (TGA). The free radical scavenging activity was measured using the DPPH• assay, and MTT cell viability assays were performed to assess cytotoxicity.</p><p><strong>Results: </strong>The results demonstrated a significant reduction in nanoparticle size from 123 nm to 116 nm and an increase in charge from -14 to -22 with rising Rutin concentrations. The formulation achieved enhanced homogeneity at a Rutin concentration of 2.0 mg/mL and showed higher stability. Incorporating Rutin improved the formulation's stability over 30 days, as evidenced by a decrease in the Differential Scanning Calorimetry peak temperature from 58.65 °C to 54.42 °C. Rutin-loaded and co-loaded nanoliposomes exhibited remarkable selectivity against PANK1 and MCF7 cell lines, with IC50 values of 2.13±0.35 μg/mL and 4.75±0.19 μg/mL, respectively.</p><p><strong>Conclusion: </strong>PEGylated Rutin-loaded nanoliposomes offer a promising platform for biodegradable and biocompatible drug delivery systems, enhancing the bioavailability, solubility, and stability of the polyphenols.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021820","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":"Anticancer Properties of Phenylboronic Acid in Androgen-Dependent (LNCaP) and Androgen-Independent (PC3) Prostate Cancer Cells via MAP Kinases by 2D and 3D Culture Methods.","authors":"Duygu Gürsoy Gürgen, Arzu Güneş, Oğuzhan Köse, Arife Ahsen Kaplan, Seda Karabulut, M Başak Tunalı, İlknur Keskin","doi":"10.2174/0118715206352302241227031015","DOIUrl":"https://doi.org/10.2174/0118715206352302241227031015","url":null,"abstract":"<p><strong>Objective: </strong>This study utilized three cell lines: normal prostate epithelial RWPE-1, androgen-dependent LNCaP, and androgen-independent PC3. We investigated the inhibitory effects of phenylboronic acid (PBA)'s inhibitory effect on cellular proliferation due to its ability to disrupt microtubule formation in prostate cancer cell lines. Additionally, this study aimed to assess the cytotoxic effects of PBA on prostate cancer cells using twodimensional (2D) and three-dimensional (3D) cell culture models.</p><p><strong>Methods: </strong>The IC50 values of PBA and colchicine were determined through viability assays in 2D and 3D models. Colony formation, proliferation, and migration assays were conducted. Immunofluorescence intensity analysis of MAPKKK proteins (ERK, JNK, p38) was performed to explore the mechanism of cellular response to PBA.</p><p><strong>Results: </strong>The IC50 values were determined for each treatment group. After 48-hour of PBA treatment, migration was inhibited more effectively than with colchicine in both cancer cell lines. After 24-hour, PBA reduced colony formation and proliferation. PBA treatment for 24-hour decreased JNK expression in PC3 and LNCaP cells in 2D models. Both PBA and colchicine increased p38 expression in PC3 spheroids. PBA's effects on cell deformation were visualized in semi-thin sections, marking the first ultrastructural observation of PBA-induced morphological defects in cancer cells.</p><p><strong>Conclusion: </strong>PBA exerts antimitotic effects by inhibiting proliferation and migration and triggers diverse metabolic responses across different cell lines. Furthermore the low toxicity of PBA's low toxicity on RWPE-1 cells suggests its potential as a promising chemotherapeutic agent for future studies.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998834","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":"Safety and Efficacy of Anlotinib-based Regimen in Patients with Unresectable or Metastatic Bone and Soft-tissue Sarcomas: A Retrospective Institutional Study.","authors":"Lina Pang, Shengli Zhang, Liye Wang, Shuai Gong, Wei He","doi":"10.2174/0118715206336884241216070930","DOIUrl":"https://doi.org/10.2174/0118715206336884241216070930","url":null,"abstract":"<p><strong>Background: </strong>Anlotinib has demonstrated durable clinical benefits in patients with unresectable or metastatic bone and soft-tissue sarcomas.</p><p><strong>Methods: </strong>92 patients treated with chemotherapy combined with or without anlotinib were collected and analyzed. The objective response rate (ORR) and disease control rate (DCR) were analyzed. Long-term survival was assessed using the Kaplan-Meier method, including median progression-free survival (mPFS) and overall survival (mOS).</p><p><strong>Results: </strong>Liposarcoma, synovial sarcoma, and rhabdomyosarcoma were the primary pathological subtypes of the 92 patients. The median age was 46 (range, 11-75) years. The ORR and DCR of the anlotinib-chemotherapy combination used as first-line therapy were 31.9% and 85.1%, respectively. However, the ORR and DCR were only 6.7% and 57.8% in the chemotherapy alone, respectively. Compared with the chemotherapy group, improvements were observed in the mPFS and mOS with anlotinib-based regimen (mPFS, 8.3 vs. 3.0 months; mOS, 59.0 vs. 22.0 months). Anlotinib-associated adverse events were well tolerated and mainly occurred in grades I and II. New anlotinib-related adverse reactions were not noted.</p><p><strong>Conclusion: </strong>Anlotinib-based regimen as a first-line therapy showed a positive effect on the treatment of unresectable or metastatic BSTSs. The anlotinib-associated adverse events were minor and well tolerated.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998750","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":"KW2478 and Cisplatin Synergistically Anti-colorectal Cancer by Targeting PI3K/AKT/mTOR Pathway.","authors":"Jianping Wang, Jun An, Lixuan Tian, Yuzi Jin, Yalei Li, Peijian Ding, Wenjing Yun, Yunpeng Zhang, Shuang Zhao","doi":"10.2174/0118715206356311241128075924","DOIUrl":"https://doi.org/10.2174/0118715206356311241128075924","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;The objective of this study is to examine the impact of KW-2478 combined with DDP on colorectal cancer cells both in vitro and in vivo and to elucidate the molecular mechanism of KW-2478 in colorectal cancer.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;qRT-PCR and Western blot were employed to assess HSP90 mRNA and protein expression in normal intestinal epithelial and colorectal cancer cells. DLD-1 and HCT116 were selected for the experiment. CCK-8 was used to detect cytotoxicity; apoptosis rate was measured using flow cytometry; Western blot was employed to measure the expression levels of apoptotic and PI3K/AKT/mTOR pathway proteins. HCT116 was used to construct a subcutaneous tumor model in nude mice. After treatment with KW-2478 and DDP, the growth rate, volume, and weight of the tumor were observed. The expression of Ki67 was detected by immunohistochemistry. Apoptosis of tumor cells was detected using TUNEL. Western blot was employed to measure the expression levels of apoptotic and PI3K/AKT/mTOR pathway proteins.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;HSP90 mRNA and protein levels were elevated in colorectal cancer cells compared to normal colorectal epithelial cells. HSP90 mRNA and protein expression levels were also significantly elevated in HCT116 and DLD-1 cells compared to other colorectal cancer cells. In DLD-1 and HCT116 cells, KW2478 and DDP inhibited cell viability. The combination of KW2478 and DDP exhibited a significantly higher inhibitory effect compared to either KW2478 or DDP alone. DDP markedly triggered apoptosis in HCT116 and DLD-1. KW2478 at 3 μg/ml and 6 μg/ml induced apoptosis in HCT116 cells but not in DLD-1 cells. The combination of KW2478 and DDP induced a significantly higher apoptosis rate as compared to either KW2478 or DDP alone. Treatment of HCT116 and DLD-1 with KW2478 or DDP alone increased Bax, Caspase9, and Caspase3 protein expression, while decreasing BCL-2. The KW2478+DDP combined treatment group exhibited more significant changes. Phosphorylation of PI3k, AKT, and mTOR decreased in the KW2478 or DDP treatment groups, with more significant changes observed in the KW2478 + DDP combination group. The growth rate, volume, and weight of subcutaneous tumors in the KW2478 or DDP treatment groups were significantly lower than control, and the KW2478+DDP combination group was more affected. Ki67 expression in subcutaneous tumors was reduced in the KW2478 or DDP treatment groups compared to the vehicle control group, with the lowest expression observed in the KW2478 + DDP combination group. The fluorescence intensity of subcutaneous tumors was higher in both the KW2478 and DDP treatment groups compared to the vehicle control group, and the KW2478 + DDP combination group exhibited the strongest fluorescence intensity among them.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The combination of KW2478 and cisplatin inhibits colorectal cancer cell proliferation and induces apoptosis by regulating the PI3K/AKT/mTOR p","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998749","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}