Chemico-Biological Interactions最新文献

{"title":"Subchronic exposure to Tamoxifen modulates the hippocampal BDNF/ERK/Akt/CREB pathway and impairs memory in intact female rats","authors":"Isabella P. Klann,&nbsp;Bruna C.W. Fulco,&nbsp;Cristina W. Nogueira","doi":"10.1016/j.cbi.2023.110615","DOIUrl":"10.1016/j.cbi.2023.110615","url":null,"abstract":"<div><p><span><span>Tamoxifen (TAM), a </span>Selective Estrogen Receptor Modulator (SERM), is commonly used to treat and prevent breast cancer. Memory impairment has been noticed in patients who experience </span>hormone therapy<span> in the case of TAM and other SERMs. Animal studies that mimic the TAM longer exposure effects are needed to better elucidate the adverse effects of continuous treatment in humans. This study evaluated the effects of TAM subchronic administration on the memory performance and hippocampal neural plasticity of intact female Wistar rats<span>. Animals were treated intragastrically with TAM (0.25 and 2.5 mg/kg) for 59 days. The rats were subjected to the Object Location Test (OLT) and Object Recognition Test (ORT) to evaluate memory performance. After euthanasia, the hippocampus samples were excised and the protein levels of the BDNF/ERK/Akt/CREB pathway were evaluated. The rat's locomotor activity and hippocampal TrkB levels were similar among the experimental groups. TAM at both doses reduced the memory performance of female rats in the OLT and short-term memory of ORT, and impaired hippocampal levels of mBDNF, proBDNF, and pCREB/CREB. TAM only at the dose of 2.5 mg/kg reduced the memory performance of rats in the long-term memory of ORT and hippocampal pERK/ERK and pAkt/Akt ratios. TAM subchronic administration induced amnesic effects and modulated the hippocampal BDNF/ERK/Akt/CREB pathway in intact young adult female Wistar rats.</span></span></p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"382 ","pages":"Article 110615"},"PeriodicalIF":5.1,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10393493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Various concentrations of hesperetin induce different types of programmed cell death in human breast cancerous and normal cell lines in a ROS-dependent manner","authors":"Mohammad Rasoul Samandari-Bahraseman ,&nbsp;Babak Khorsand ,&nbsp;Sara Zareei ,&nbsp;Massoud Amanlou ,&nbsp;Hanieh Rostamabadi","doi":"10.1016/j.cbi.2023.110642","DOIUrl":"10.1016/j.cbi.2023.110642","url":null,"abstract":"<div><p><span>The polyphenolic component of citrus fruits, hesperetin<span> (Hst), is a metabolite of hesperidin<span><span>. In this study, we examined the effect of varying doses and exposure times of hesperetin on MCF-7 and MDA-MB-231 cancer cells, as well as MCF-10A normal cells. By using MTT assay, real-time PCR, western blot, and flow cytometry, we determined the effects of Hst on </span>cell viability<span>, ROS levels, and markers of cell death. Furthermore, molecular docking was used to identify Hst targets that might be involved in ROS-dependent cell death. According to the results, different concentrations of Hst induced different modes of cell death at specific ROS levels. Paraptosis occurred in all cell lines at concentration ranges of IC</span></span></span></span>₃₅ to IC₆₀, and apoptosis occurred at concentrations greater than IC₆₅. In addition, MDA-MB-231 cells were subjected to senescence at sub-toxic doses when treated for a long period of time. When Hst levels were higher, <em>N</em>-acetylcysteine (NAC)'s effect on neutralizing ROS was more pronounced. According to the docking results, Hst may interact with several proteins involved in the regulation of ROS. As an example, the interaction of CCS (Copper chaperone for superoxide dismutase) with Hst might interfere with its chaperone function in folding SOD-1 (superoxide dismutase enzyme), contributing to an increase in cytoplasmic ROS levels. Finally, depending on the ROS level, Hst induces various modes of cell death.</p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"382 ","pages":"Article 110642"},"PeriodicalIF":5.1,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10393536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Swainsonine inhibits autophagic degradation and causes cytotoxicity by reducing CTSD O-GlcNAcylation","authors":"Shuai Wang ,&nbsp;Panpan Tan ,&nbsp;Hongwei Wang ,&nbsp;Jicang Wang ,&nbsp;Cai Zhang ,&nbsp;Hao Lu ,&nbsp;Baoyu Zhao","doi":"10.1016/j.cbi.2023.110629","DOIUrl":"10.1016/j.cbi.2023.110629","url":null,"abstract":"<div><p><span>Swainsonine (SW) is the primary toxin in locoweed, a poisonous plant. SW can cause animal poisoning, affect the quality and safety of meat products and threaten human health, but the mechanism of its toxicity is little defined. Here, we identified 159 differentially expressed proteins, many of which are involved in autophagy and glycosylation modification processes, using proteomics<span> sequencing analysis. O-linked-N-acetylglucosamylation (O-GlcNAcylation) is a glycosylation modification widely involved in various biological processes. Our results show that SW toxicity is related to O-GlcNAcylation. In addition, increased O-GlcNAcylation with the O-GlcNAcase (OGA) inhibitor TMG promoted autophagy, while decreased O-GlcNAcylation with the O-GlcNAc transferase (OGT) inhibitor OSMI inhibited autophagy. Further analysis by Immunoprecipitation </span></span><strong>(</strong><span>IP) showed that SW could change the O-GlcNAcylation of Cathepsin D<span> (CTSD), reducing the expression of mature CTSD (m-CTSD). In summary, these findings suggest that SW inhibits the O-GlcNAcylation of CTSD, affecting its maturation and leading to the impairment of lysosome<span> function. Consequently, it inhibits autophagy degradation, and causes cytotoxicity, providing a new theoretical basis for SW toxicological mechanism.</span></span></span></p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"382 ","pages":"Article 110629"},"PeriodicalIF":5.1,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10009121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resveratrol triggers the ER stress-mediated intrinsic apoptosis of neuroblastoma cells coupled with suppression of Rho-dependent migration and consequently prolongs mouse survival","authors":"Ding-Ping Sun ,&nbsp;Jui-Tai Chen ,&nbsp;Shun-Tai Yang ,&nbsp;Tso-Hsiao Chen ,&nbsp;Shing-Hwa Liu ,&nbsp;Ruei-Ming Chen","doi":"10.1016/j.cbi.2023.110645","DOIUrl":"10.1016/j.cbi.2023.110645","url":null,"abstract":"<div><p><span>Neuroblastoma, the most common childhood tumor, are highly malignant and fatal because neuroblastoma cells extremely defend against apoptotic targeting. Traditional treatments for neuroblastomas are usually ineffective and lead to serious side effects and poor prognoses. In this study, we investigated the molecular mechanisms of resveratrol-induced insults to neuroblastoma cells and survival extension of </span>nude mice<span><span><span> with neuroblastomas, especially in the endoplasmic reticular (ER) stress-intracellular reactive oxygen species (iROS) axis-mediated signals. Resveratrol specifically killed neuroblastoma cells mainly via apoptosis and autophagy rather than necrosis. As to the mechanisms, </span>resveratrol time-dependently triggered productions of </span>Grp78<span><span> protein and iROS in neuroblastoma cells. Attenuating the ER stress-iROS signaling axis significantly suppressed resveratrol-induced autophagy, DNA damage, and cell apoptosis. Successively, resveratrol decreased phosphorylation of retinoblastoma protein and induced cell cycle arrest at the S phase, translocation of </span>Bak protein<span> to mitochondria, a reduction in the mitochondrial membrane potential, cascade activation of caspases-9, -3, and -6, and DNA fragmentation. Moreover, weakening the ER stress-iROS axis concomitantly overcome resveratrol-induced decreases in translocation of Rho protein to membranes and succeeding cell migration. Interestingly, administration of resveratrol did not cause significant side effects but could protect the neuroblastoma-bearing nude mice from body weight loss and consequently extended the animal survival. In parallel, resveratrol elevated levels of Grp78 and then induced cell apoptosis in neuroblastoma tissues. This study has shown that resveratrol could kill neuroblastoma cells and extend survival of animals with neuroblastomas by triggering the ER stress-iROS-involved intrinsic apoptosis and suppression of Rho-dependent cell migration. Our results imply the potential of resveratrol as a drug candidate for chemotherapy of neuroblastoma patients.</span></span></span></p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"382 ","pages":"Article 110645"},"PeriodicalIF":5.1,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10009561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molybdenum and/or cadmium induce NLRP3 inflammasome production by causing mitochondria-associated endoplasmic reticulum membrane dysfunction in sheep hepatocytes","authors":"Huifeng Chang ,&nbsp;Fan Yang ,&nbsp;He Bai ,&nbsp;Zengting Lu ,&nbsp;Chenghong Xing ,&nbsp;Xueyan Dai ,&nbsp;Wengen Wan ,&nbsp;Shuxian Liao ,&nbsp;Huabin Cao","doi":"10.1016/j.cbi.2023.110617","DOIUrl":"10.1016/j.cbi.2023.110617","url":null,"abstract":"<div><p><span><span>Accumulation of the heavy metals molybdenum (Mo) and cadmium (Cd) in the liver can induce organelle damage and inflammation, resulting in hepatotoxicity. The effect of Mo and/or Cd on sheep hepatocytes was investigated by determining the relationship between the mitochondria-associated </span>endoplasmic reticulum<span><span> membrane (MAM) and NLRP3 inflammasome<span>. Sheep hepatocytes were divided into four groups: the control group, Mo group (600 μM Mo), Cd group (4 μM Cd) and Mo + Cd group (600 μM Mo+4 μM Cd). The results showed that Mo and/or Cd exposure increased the levels of lactate dehydrogenase (LDH) and </span></span>nitric oxide (NO) in the cell culture supernatant, elevated the levels of intracellular Ca</span></span>²⁺ and mitochondrial Ca²⁺<span>, downregulated the expression of MAM-related factors (IP3R, GRP75, VDAC1, PERK, ERO1-α, Mfn1, Mfn2, ERP44), shortened the length of the MAM and reduced the formation of the MAM structure, eventually causing MAM dysfunction. Moreover, the expression levels of NLRP3 inflammasome-related factors (NLRP3, Caspase1, IL-1β, IL-6, TNF-α) were also dramatically increased after Mo and Cd exposure, triggering NLRP3 inflammasome production. However, an IP3R inhibitor, 2-APB treatment significantly alleviated these changes. Overall, the data indicate that Mo and Cd coexposure leads to structural disruption and dysfunction of MAM, disrupts cellular Ca</span>²⁺<span> homeostasis, and increases NLRP3 inflammasome production in sheep hepatocytes. However, the inhibition of IP3R alleviates NLRP3 inflammasome production induced by Mo and Cd.</span></p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"382 ","pages":"Article 110617"},"PeriodicalIF":5.1,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10015542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glabridin plays dual action to intensify anti-metastatic potential of paclitaxel via impeding CYP2C8 in liver and CYP2J2/EETs in tumor of an orthotopic mouse model of breast cancer","authors":"Ashiya Jamwal ,&nbsp;Jagdish Chand ,&nbsp;Anshurekha Dash ,&nbsp;Shipra Bhatt ,&nbsp;Sumit Dhiman ,&nbsp;Priya Wazir ,&nbsp;Buddh Singh ,&nbsp;Anindya Goswami ,&nbsp;Utpal Nandi","doi":"10.1016/j.cbi.2023.110605","DOIUrl":"10.1016/j.cbi.2023.110605","url":null,"abstract":"<div><p><span>In spite of unprecedented advances in modern cancer therapy, there is still a dearth of targeted therapy to circumvent triple-negative breast cancer (TNBC). Paclitaxel<span> is the front-line therapy against TNBC, but the main constraints of its treatment are dose-related adverse effects and emerging chemoresistance. In this context, glabridin (phytoconstituent from </span></span><span><em>Glycyrrhiza glabra</em></span>) is reported to hit multiple signalling pathways at the <em>in-vitro</em> level, but hardly any information is known at the <em>in-vivo</em><span><span><span> level. We aimed here to elucidate glabridin potential with an underlying mechanism in combination with a low dose of paclitaxel using a highly aggressive mouse mammary carcinoma<span> model. Glabridin potentiated the anti-metastatic efficacy of paclitaxel by substantially curtailing tumor burden and diminishing lung nodule formation. Moreover, glabridin remarkably attenuated epithelial-mesenchymal transition (EMT) traits of hostile cancer cells via up-regulating (E-cadherin &amp; occludin) and down-regulating (Vimentin &amp; Zeb1) vital EMT markers. Besides, glabridin amplified apoptotic induction effect of paclitaxel in tumor tissue by declining or elevating pro-apoptotic (Procaspase-9 or Cleaved Caspase-9 &amp; Bax) and reducing anti-apoptotic (Bcl-2) markers. Additionally, concomitant treatment of glabridin and paclitaxel predominantly lessened </span></span>CYP2J2<span> expression with marked lowering of epoxyeicosatrienoic acid (EET)'s levels in tumor tissue to reinforce the anti-tumor impact. Simultaneous administration of glabridin with paclitaxel notably enhanced plasma exposure and delayed clearance of paclitaxel, which was mainly arbitrated by CYP2C8-mediated slowdown of paclitaxel metabolism in the liver. The fact of intense </span></span>CYP2C8<span> inhibitory action of glabridin was also ascertained using human liver microsomes. Concisely, glabridin plays a dual role in boosting anti-metastatic activity by augmenting paclitaxel exposure via CYP2C8 inhibition-mediated delaying paclitaxel metabolism and limiting tumorigenesis via CYP2J2 inhibition-mediated restricting EETs level. Considering the safety, reported protective efficacy, and the current study results of boosted anti-metastatic effects, further investigations are warranted as a promising neoadjuvant therapy for crux paclitaxel chemoresistance and cancer recurrence.</span></span></p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"382 ","pages":"Article 110605"},"PeriodicalIF":5.1,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10018332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carbon nanotubes: Structural defects as stressors inducing lung cell toxicity","authors":"Rossella Daniela Bengalli ,&nbsp;Giuseppe Zerbi ,&nbsp;Andrea Lucotti ,&nbsp;Tiziano Catelani ,&nbsp;Paride Mantecca","doi":"10.1016/j.cbi.2023.110613","DOIUrl":"10.1016/j.cbi.2023.110613","url":null,"abstract":"<div><p><span><span>Lung toxicity<span> of carbon nanotubes<span> (CNTs) is matter of concern since very long time. However, their mechanism of toxicity is still not yet well defined. In this work, the role of structural defects as organic stressors of CNTs able to trigger their potential toxicity is investigated. Four commercial CNTs, with different carbon purity grade, are morphologically characterized by transmission electron microscopy (TEM) and the relative amount of structural defects are estimated through </span></span></span>Raman spectroscopy, by measuring the intensity ratio D/G (I</span>_D/I_G<span>). The oxidative potential of CNTs is evaluated with cytochrome-C assay and reactive oxygen species (ROS) detection. Data show that CNTs with larger amounts of structural defects (higher I</span>_D/I_G<span> ratio) induce an increased ROS generation and consequent cytotoxicity and cellular damage, shown by TEM images of CNTs-cells interaction. Raman analyses of cells exposed to CNTs point out that the spectra of the CNTs inside the cells show no differences with respect of the signal recorded for cell-free CNTs, evidencing their biopersistence in lung cells. Raman spectra cannot provide direct indication of the existence of metals as impurity. It follows that the intensity ratio I</span>_D/I_G can be taken as a predictive marker of the toxicity of a given CNT.</p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"382 ","pages":"Article 110613"},"PeriodicalIF":5.1,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10024431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multidisciplinary docking, kinetics and X-ray crystallography studies of baicalein acting as a glycogen phosphorylase inhibitor and determination of its’ potential against glioblastoma in cellular models","authors":"Rachel T. Mathomes ,&nbsp;Symeon M. Koulas ,&nbsp;Ioannis Tsialtas ,&nbsp;George Stravodimos ,&nbsp;Philip J. Welsby ,&nbsp;Anna-Maria G. Psarra ,&nbsp;Izabela Stasik ,&nbsp;Demetres D. Leonidas ,&nbsp;Joseph M. Hayes","doi":"10.1016/j.cbi.2023.110568","DOIUrl":"10.1016/j.cbi.2023.110568","url":null,"abstract":"<div><p>Glycogen phosphorylase (GP) is the rate-determining enzyme in the glycogenolysis pathway. Glioblastoma (GBM) is amongst the most aggressive cancers of the central nervous system. The role of GP and glycogen metabolism in the context of cancer cell metabolic reprogramming is recognised, so that GP inhibitors may have potential treatment benefits. Here, baicalein (5,6,7-trihydroxyflavone) is studied as a GP inhibitor, and for its effects on glycogenolysis and GBM at the cellular level. The compound is revealed as a potent GP inhibitor against human brain GPa (<em>K</em>_<em>i</em> = 32.54 μM), human liver GPa (<em>K</em>_<em>i</em> = 8.77 μM) and rabbit muscle GPb (<em>K</em>_<em>i</em> = 5.66 μM) isoforms. It is also an effective inhibitor of glycogenolysis (<em>IC</em>_<em>50</em> = 119.6 μM), measured in HepG2 cells. Most significantly, baicalein demonstrated anti-cancer potential through concentration- and time-dependent decrease in cell viability for three GBM cell-lines (U-251 MG, U-87 MG, T98-G) with <em>IC</em>_<em>50</em> values of ∼20–55 μM (48- and 72-h). Its effectiveness against T98-G suggests potential against GBM with resistance to temozolomide (the first-line therapy) due to a positive O⁶-methylguanine-DNA methyltransferase (MGMT) status. The solved X-ray structure of rabbit muscle GP–baicalein complex will facilitate structure-based design of GP inhibitors. Further exploration of baicalein and other GP inhibitors with different isoform specificities against GBM is suggested.</p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"382 ","pages":"Article 110568"},"PeriodicalIF":5.1,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0009279723002351/pdfft?md5=53574a34233139828702002b417401da&pid=1-s2.0-S0009279723002351-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10371848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginsenosides in cancer: Targeting cell cycle arrest and apoptosis","authors":"Muhammad Ajmal Shah ,&nbsp;Syed Muhammad Abuzar ,&nbsp;Kainat Ilyas ,&nbsp;Irtaza Qadees ,&nbsp;Momna Bilal ,&nbsp;Rimsha Yousaf ,&nbsp;Roaa Mohammed Tahir Kassim ,&nbsp;Azhar Rasul ,&nbsp;Uzma Saleem ,&nbsp;Maria Silvana Alves ,&nbsp;Haroon Khan ,&nbsp;Renald Blundell ,&nbsp;Philippe Jeandet","doi":"10.1016/j.cbi.2023.110634","DOIUrl":"10.1016/j.cbi.2023.110634","url":null,"abstract":"<div><p><span><span><span>Despite the existence of extensive clinical research and novel therapeutic treatments, cancer remains undefeated and the significant cause of death worldwide. Cancer is a disease in which growth of cells goes out of control, being also able to invade other parts of the body. Cellular division is strictly controlled by multiple checkpoints like G1/S and G2/M which, when dysregulated, lead to uncontrollable cell division. The current remedies which are being utilized to combat cancer are </span>monoclonal antibodies<span>, chemotherapy, cryoablation, and bone marrow transplant etc. and these have also been greatly disheartening because of their serious adverse effects like hypotension, neuropathy, necrosis, </span></span>leukemia relapse and many more. Bioactive compounds derived from natural products have marked the history of the development of novel drug therapies against cancer among which ginsenosides have no peer as they target several signaling pathways, which when abnormally regulated, lead to cancer. Substantial research has reported that ginsenosides like Rb1, Rb2, Rb3, Rc, Rd, Rg3, Rh2 etc. can prevent and treat cancer by targeting different pathways and molecules by induction of autophagy, neutralizing ROS, induction of cancerous cell death by controlling the p53 pathway, modulation of </span>miRNAs<span> by decreasing Smad2 expression, regulating Bcl-2 expression by normalizing the NF-Kb pathway, inhibition of inflammatory pathways by decreasing the production of cytokines like IL-8, causing cell cycle arrest by restricting cyclin E1 and CDC2, and induction of apoptosis during malignancy by decreasing β-catenin levels etc. In this review, we have analyzed the anti-cancer therapeutic potential of various ginsenoside compounds in order to consider their possible use in new strategies in the fight against cancer.</span></p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"382 ","pages":"Article 110634"},"PeriodicalIF":5.1,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10372346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research progress of small-molecule drugs in targeting telomerase in human cancer and aging","authors":"Ziyi Shen ,&nbsp;Yuanhui Wang ,&nbsp;Guanzhen Wang ,&nbsp;Wei Gu ,&nbsp;Shengchao Zhao ,&nbsp;Xiaomeng Hu ,&nbsp;Wei Liu ,&nbsp;Yi Cai ,&nbsp;Zhihong Ma ,&nbsp;Rupesh K. Gautam ,&nbsp;Jia Jia ,&nbsp;Chunpeng (Craig) Wan ,&nbsp;Tingdong Yan","doi":"10.1016/j.cbi.2023.110631","DOIUrl":"10.1016/j.cbi.2023.110631","url":null,"abstract":"<div><p><span>Telomeres are unique structures located at the ends of linear chromosomes, responsible for stabilizing chromosomal structures. They are synthesized by telomerase<span>, a reverse transcriptase<span> ribonucleoprotein complex. Telomerase activity is generally absent in human somatic cells, except in stem cells and germ cells. Every time a cell divides, the telomere sequence is shortened, eventually leading to replicative senescence and cell apoptosis when the telomeres reach a critical limit. However, most human cancer cells exhibit increased telomerase activity, allowing them to divide continuously. The importance of telomerase in cancer and aging has made developing </span></span></span>drugs targeting telomerase a focus of research. Such drugs can inhibit cancer cell growth and delay aging by enhancing telomerase activity in telomere-related syndromes or diseases. This review provides an overview of telomeres, telomerase, and their regulation in cancer and aging, and highlights small-molecule drugs targeting telomerase in these fields.</p></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"382 ","pages":"Article 110631"},"PeriodicalIF":5.1,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10393520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}