Expression Of HSPA1A Research Articles

Abstract 4327: Disruption of aggregated oncogenic mutant p53 as a novel therapeutic strategy for gynecologic cancers

Abstract High grade serous ovarian and endometrial cancers possess TP53 missense mutations that result in loss of the central tumor suppressive functions of wild type p53 (WT p53). In normal unstressed cells, p53 protein is regulated through ubiquitin-tagging and shuttling to the 26S proteasome by the E3 ubiquitin ligase MDM2 (Murine Double Minute 2). In cancer cells with mutant forms of p53, MDM2 is not adequately expressed in such cells to perform its regulatory role, thus leading to mutant p53 aggregates. Understanding mechanisms to target mutant p53 proteins for degradation in cancers has tremendous therapeutic potential. Recent discoveries in p53 refolding agents to reinstate WT p53 functionality for the treatment of gynecologic malignancies have shown promise. Treatment of cancer cells harboring p53 mutations with p53 reactivators HO-3867 and our novel curcumin analogue AKT-100 displayed an upregulated expression of heat shock protein 70 (HSP70) family member genes, as well as the autophagy-inducing co-chaperone BAG3 (Bcl-2-associated athanogene 3) by RNA sequencing analysis. Western blot analysis showed a decrease in p53 protein expression after treatment with the curcumin analogues, while MDM2 levels were unchanged, indicating an alternative mechanism of mutant p53 degradation. We hypothesize that the BAG3-HSP70 interaction varies with different mutations in p53 as well as the various HSP70 family members involved and can be therapeutically normalized to restore WT p53 regulation. Using our cell models of high grade serous ovarian and endometrial cancer, we have determined through co-immunoprecipitation and mass spectrometry that p53 binds HSPA6 and BAG3 upon treatment only with AKT-100 in KLE (p53 R175H) and COV362 (p53 Y220C) cells. Furthermore, co-treatment of curcumin analogue AKT-100 plus HSP inhibitor SHetA2 (sulfur heteroarotinoid A2, NSC 726189) highly increased the expression of BAG3, HSPA1A, HSPA6 and ubiquitination while decreasing mutant p53 expression in KLE cells. Confocal microscopy in KLE cells also displayed a shift of mutant p53 and HSPA6 from nuclear to mostly cytoplasmic upon treatment with AKT-100. Co-treatment with AKT-100 and SHetA2 highly increased HSPA6 expression throughout the cell, while p53 returned to the nucleus to perform normal apoptotic functions based on CyQuant proliferation data. Our data indicates a novel mechanistic insight into therapeutically intervening to re-establish normal p53 levels and regulation to treat women with advanced, mutant p53 gynecologic malignancies. Citation Format: Geneva L. Williams, Jamie L. Padilla, Lane E. Smith, Jun-yong Choe, Doris M. Benbrook, Kimberly K. Leslie. Disruption of aggregated oncogenic mutant p53 as a novel therapeutic strategy for gynecologic cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4327.

Network Pharmacology Integrated Experimental Validation Uncover Quercetin as the Key Ingredient of Hedyotis diffusa Anti-BRCA.

Hedyotis diffusa, a famous Traditional Chinese Medicine (TCM), has been extensively used clinically for thousands of years. Although the therapeutic effect of Hedyotis diffusa on tumors has attracted wide attention, components, and mechanisms against breast cancer (BRCA) have not been fully understood. The study aims to explore the active components and molecular mechanisms of Hedyotis diffusa against BRCA using network pharmacology combined with experimental validation. The results of network pharmacology indicated that quercetin was the most core component of Hedyotis diffusa. BIRC5, CDK1, FOS, and HSP90AA1 were considered candidate key targets of Hedyotis diffusa against BRCA. KEGG enrichment analysis revealed that multiple cancer-related pathways are enriched, including pathways in cancer, estrogen signaling pathway, and PI3K-AKT signaling pathway, and the like. The results of invitro experiments showed that quercetin inhibited the proliferation of both MCF-7 cells and MDA-MB-231 cells in a dose-dependent manner. Furthermore, the experimental data demonstrated quercetin may decrease the expression level of BIRC5, CDK1, and HSP90AA1 in MCF-7 cells. Overall, results of the study indicated that quercetin may play a vital role in the anti-BRCA effect of Hedyotis diffusa, and quercetin can affect the expression of BIRC5, CDK1, and HSP90AA1 in MCF-7 cells. This study may provide new evidence for the use of Hedyotis diffusa in the treatment of BRCA.

Exploring the protective mechanisms of syringaresinol against myocardial infarction by experimental validation and network pharmacology.

Exploring the protective mechanisms of syringaresinol against myocardial infarction by experimental validation and network pharmacology.

Perillaldehyde ameliorates sepsis-associated acute kidney injury via inhibiting HSP90AA1-mediated ferroptosis and pyroptosis: Molecular structure and protein interaction of HSP90AA1.

Perillaldehyde ameliorates sepsis-associated acute kidney injury via inhibiting HSP90AA1-mediated ferroptosis and pyroptosis: Molecular structure and protein interaction of HSP90AA1.

Unveiling the Novel Anti - Tumor Potential of Digitonin, a Steroidal Saponin, in Gastric Cancer: A Network Pharmacology and Experimental Validation Study.

Gastric cancer (GC) remains a leading cause of cancer-related mortality, with limited effective treatment options for advanced stages. As a steroidal saponin with documented anti-neoplastic properties in multiple cancers, digitonin's mode of action in GC pathogenesis has yet to be fully elucidated. This research focused on exploring the potential of Digitonin in GC treatment using a combination of network pharmacology and experimental validation. The inhibitory effects of Digitonin on the proliferation, invasion, and migration of gastric cancer cells were evaluated using CCK-8, colony formation, wound healing, and transwell assays. Key targets of Digitonin were identified through network pharmacology. Molecular docking and various experiments, including Western blot, immunofluorescence, and a subcutaneous xenograft model, were used for validation. Digitonin exhibited stronger cytotoxicity against GC cells and significantly inhibited GC cell proliferation, migration, and invasion. Network pharmacology analysis revealed that the core targets of Digitonin are involved in key cancer-related signaling pathways, including HIF-1α, Ras, and PI3K-Akt pathways, with HSP90AA1 and NFKB1 identified as central targets. Further molecular docking, Western blotting, and immunofluorescence experiments confirmed that Digitonin significantly suppressed the expression of HSP90AA1 and inhibited the nuclear translocation of NFKB1, inducing cell apoptosis. Additionally, a subcutaneous xenograft model of GC further validated that Digitonin effectively inhibited tumor growth. Digitonin serves as a promising multi-target therapeutic agent for GC. This study underscores the potential of combining network pharmacology with traditional Chinese medicine to identify novel therapeutic targets and develop effective anti-cancer strategies. In addition, these findings suggest that digitonin could be a promising candidate for future clinical trials in GC treatment.

Mulberrin suppresses gastric cancer progression and enhances chemosensitivity to oxaliplatin through HSP90AA1/PI3K/AKT axis.

Mulberrin suppresses gastric cancer progression and enhances chemosensitivity to oxaliplatin through HSP90AA1/PI3K/AKT axis.

Network pharmacology and experimental analysis reveal Ethyl caffeate delays osimertinib resistance in lung cancer by suppression of MET

BackgroundFei Yanning Formula (FYN) is extensively applied in clinical lung cancer treatment. However, the specific active constituents and targets of its therapeutic effects remain unclear.ObjectiveThe study aims to explore the active constituents and mechanism of FYN in delaying osimertinib resistance by network pharmacology analysis and experimental verification.MethodsWe collected the chemical constituents of the FYN based on the TCMSP database and relevant literature sources. Osimertinib resistance-related targets were acquired from the GeneCards database. We systematically construct the PPI network and KEGG analysis to explore hub targets and key pathways. The main active components of FYN were identified by molecular docking. Subsequently, we conducted in vitro experiments to verify its effect on osimertinib-resistant cells in lung cancer.ResultsThe PPI network and KEGG pathways analysis revealed six key targets linked to PI3K-AKT signaling pathways (ERBB2, EGFR, MET, HSP90AA1, MCL1, and IGF1R). RT-qPCR and immunohistochemical analyses demonstrated that FYN could suppress the expression of ERBB2, MET and HSP90AA1. Molecular docking indicated that Ethyl caffeate, the primary component in FYN, had a stronger binding ability with MET. Experiments illustrated that Ethyl caffeate inhibited the migration and proliferation of osimertinib-resistant cells, promoted apoptosis, and suppressed the expression level of MET.ConclusionFYN might delay osimertinib resistance by downregulating the expression of MET, which can be attributed to its active ingredient, Ethyl caffeate.

The Anti-PEDV Effects and Mechanisms of Forsythia Essential Oil Based on Network Pharmacology and Experimental Validation.

Porcine epidemic diarrhea virus (PEDV), a member of the Coronaviridae, is responsible for acute diarrhea, vomiting, and dehydration, which can lead to high mortality in neonatal piglets. Previous research has indicated the antiviral potential of forsythia essential oil (FEO); however, its active components and mechanisms of action remain inadequately defined. This study aims to investigate the antiviral effects of FEO and elucidate its potential mechanisms for treating PEDV. The primary components of FEO were identified using gas chromatography-mass spectrometry (GC/MS) in conjunction with the National Institute of Standards and Technology Standard Spectrum (NIST) Database. Network pharmacology and weighting coefficients were employed to determine the key signaling pathways associated with PEDV-related diseases. Molecular docking simulations were conducted to explore the interactions between the active ingredients and their corresponding targets. The safety profile of FEO was assessed through cell viability assays utilizing the CCK8 method. Subsequently, immunofluorescence assays (IFA) and reverse transcription-quantitative polymerase chain reaction (RT-Q-PCR) were performed to provide evidence of the anti-PEDV effects. Additionally, the viral replication cycle was analyzed to identify the stages at which FEO exerts its antiviral effects. Finally, key targets were validated through RT-Q-PCR to further investigate the anti-PEDV mechanisms of FEO. The IL-17 signaling pathway was identified as a critical pathway for the treatment of PEDV with FEO based on network pharmacology and weighting coefficient analyses. Furthermore, results from RT-Q-PCR and IFA demonstrated that FEO influenced the replication of PEDV during the attachment and internalization phases. Specifically, during the viral attachment phase, FEO significantly upregulated the expression of HSP90AA1 while downregulating MAPK14 expression, leading to a reduction in associated inflammatory factors. At the high dose of FEO, the expression of HSP90AA1 was higher than that of the model group by about 5-fold, and the expression of MAPK14 was lower than that of the model group by about 2-fold. Cell viability assay showed no significant cytotoxicity of FEO at 0.63 μL/mL, thus confirming its safety. The findings of this study suggest that FEO possesses potential antiviral properties against PEDV. Its novel mechanisms of action warrant further investigation, which may contribute to the development of effective therapeutic strategies for managing PEDV infections.

Bisdemethoxycurcumin mitigates traumatic brain injury in rats by modulating autophagy and oxidative stress via heat shock protein 90 alpha family class A member 1-mediated nuclear translocation of transcription factor EB.

Bisdemethoxycurcumin mitigates traumatic brain injury in rats by modulating autophagy and oxidative stress via heat shock protein 90 alpha family class A member 1-mediated nuclear translocation of transcription factor EB.

N6-methyladenosine (m6A) modification regulates HSPA1A and HSPA1B expression in Müller cells under high glucose stress.

N6-methyladenosine (m6A) modification regulates HSPA1A and HSPA1B expression in Müller cells under high glucose stress.

Design, Synthesis, and Antitumor Activity of Novel Eupatilin Derivatives Based on the Mannich Reaction.

Eupatilin, a natural bioactive flavone, is the active ingredient in traditional Chinese medicine Artemisia argyi Levl. et Vant. To enhance the antitumor effect of eupatilin, we designed a series of novel eupatilin-Mannich derivatives and investigated antitumor activity against several human cancer cell lines, including gastric cancer cells (AGS), esophageal cancer cells (Eca-109), and breast cancer cells (MDA-MB-231). Among all derivatives, the majority demonstrated superior antitumor activity compared to eupatilin, with compound 3d exhibiting the most effective antitumor activity against AGS cells. Furthermore, compound 3d effectively inhibited colony formation and migration of AGS cells. Network pharmacology combined with molecular docking studies indicated that compound 3d exerts antitumor activity by targeting the Hsp90AA1 and multiple signaling pathways. In addition, the Western blot experiment results showed that compound 3d reduced the expression of Hsp90AA1 in AGS cells, indicating that Hsp90AA1 may be the potential target of compound 3d. In summary, several novel eupatilin derivatives were prepared via the Mannich reaction, representing the first structure modification study of eupatilin. The mechanism of action of compound 3d was estimated through cell experiments, network pharmacology, molecular docking, and Western blot experiments, to provide lead compounds for the discovery of natural product-based antitumor candidates.

Molecular response of canine testis to GnRH agonist: Insights into AR, HIF-1α, and HSPs expression during arrest and recovery of spermatogenesis.

Molecular response of canine testis to GnRH agonist: Insights into AR, HIF-1α, and HSPs expression during arrest and recovery of spermatogenesis.

Identification of key genes associated with oxidative stress in ischemic stroke via bioinformatics integrated analysis

BackgroundIschemic stroke (IS) is a common cerebrovascular disease. Although the formation of atherosclerosis, which is closely related to oxidative stress (OS), is associated with stroke-related deaths. However, the role of OS in IS is unknown.MethodsOS-related key genes were obtianed by overlapping the differentially expressed genes (DEGs) between IS and normal control (NC) specimens, IS-related genes, and OS-related genes. Then, we investigated the mechanism of action of key genes. Subsequently, protein–protein interaction (PPI) network and machine learning algorithms were utilized to excavate feature genes. In addition, the network between feature genes and microRNAs (miRNAs) was established to investigate the regulatory mechanism of feature genes. Finally, quantitative PCR (qPCR) was utilized to validate the expression of feature genes with blood specimens.ResultsA total of 42 key genes related to OS were acquired. Enrichment analysis indicated that the key genes were associated with oxidative stress, reactive oxygen species, lipid and atherosclerosis, and cell migration-related pathways. Then, 6 feature genes (HSPA8, NCF2, FOS, KLF4, THBS1, and HSPA1A) related to OS were identified for IS. Besides, 6 feature genes and 255 miRNAs were utilized to establish a feature genes-miRNA network which contained 261 nodes and 277 edges. At last, qPCR results revealed that there was a trend for higher expression of FOS, KLF4, and HSPA1A in IS specimens than in NC specimens. Additionally, HSPA8 expression was significantly decreased in the IS specimens, which was consistent with the findings of the GEO database analysis.ConclusionIn conclusion, 6 feature genes (HSPA8, NCF2, FOS, KLF4, THBS1, and HSPA1A) related to OS were mined by bioinformatics analysis, which might provide a new insights into the evaluation and treatment of IS.Clinical trial number: Not applicable.

Effect and Mechanism of Aloin in Ameliorating Chronic Prostatitis/Chronic Pelvic Pain Syndrome: Network Pharmacology and Experimental Verification.

This research aims to investigate the role and potential mechanisms of Aloin in Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) through network pharmacology and experimental approaches. Using network pharmacology methods, potential targets of Aloin and targets related to CP/CPPS were screened from public databases. The protein-protein interaction (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to predict the core targets and pathways of Aloin against CP/CPPS. The effects of Aloin in ameliorating CP/CPPS were verified in animal experiments. A total of 235 genes interacting with Aloin in CP/CPPS were identified. PPI network analysis revealed five core targets: AKT1, EGFR, ESR1, HSP90AA1, and SRC. GO analysis yielded 2916 enrichment results, with 2562 related to Biological Process (BP), 94 to Cellular Component (CC), and 260 to Molecular Function (MF). KEGG pathway analysis identified 172 pathways. Molecular docking confirmed stable binding between Aloin and core targets. Molecular dynamics simulations further validated binding stability by analyzing Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), Radius of Gyration (Rg), hydrogen bonds, Solvent Accessible Surface Area (SASA), and Gibbs free energy of Aloin-target complexes. Experimental validation showed that Aloin alleviated pain, reduced inflammatory factors, and decreased oxidative stress in a rat model of CP/CPPS. The qRT-PCR results showed that Aloin intervention reduced the mRNA expression of AKT1, EGFR, HSP90AA1, and SRC, while increasing ESR1 mRNA expression. These changes may underlie its therapeutic effects in CP/CPPS. Our study revealed that Aloin exerts a beneficial effect on mitigating the pain symptoms associated with CP/CPPS, ameliorating inflammation, and reducing oxidative stress. Through network pharmacology, potential targets and signaling pathways were identified, suggesting the therapeutic promise of Aloin for CP/CPPS. These findings advocate for further exploration into its clinical efficacy and mechanistic underpinnings in the treatment of CP/CPPS.

Systematic pharmacology-based strategy to investigate the mechanism of beta-sitosterol for the treatment of rheumarthritis.

Objective: β-Sitosterol, which is derived from Vladimiriae Radix (VR), is used for the treatment of rheumatoid arthritis (RA), but the pharmacological mechanisms through which β-sitosterol affects RA have not been fully elucidated. Methods: Through the Traditional Chinese Medicine Systems Pharmacology and Analysis (TCMSP), PubChem, SwissTargetPrediction, GeneCards, DisGeNET, and OMIM databases, "β-sitosterol-RA"-related genes were obtained, and a target protein interaction network (protein-protein interaction [PPI]) was constructed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out for the intersecting genes. Discovery Studio 2019 software was used to perform molecular docking on MMP9, CASP3, HSP90AA1, SRC, EGFR, and ALB genes. β-Sitosterol was co-cultured with MH7A cells in three experimental groups: control group (DMSO), positive drug group (methotrexate, 80μmol/L), and drug intervention group (10, 20, 40, 80, and 160μmol/L β-sitosterol). The CCK8 method was used to investigate the inhibitory effect of β-sitosterol on the proliferation of MH7A cells. RT-PCR was used to analyze the mRNA expression of the abovementioned core targets. Results: A total of 41 genes associated with β-sitosterol and RA were obtained, mainly involving the FoxO signaling pathway and PI3K/AKT signaling pathway. The molecular docking results suggested that β-sitosterol could bind effectively to six core targets. The experimental results showed that β-sitosterol could significantly inhibit the excessive proliferation of MH7A cells (p< 0.05). The RT-PCR results showed that the expression of MMP9, HSP90AA1, SRC, EGFR, and ALB core genes in the control group was significantly upregulated, while the CASP3 gene was downregulated. Compared to the control group, the mRNA expression of MMP9, HSP90AA1, SRC, EGFR, and ALB decreased (p< 0.01), while the apoptosis-related gene CASP3 increased in both the drug intervention (80μmol/L β-sitosterol) and positive drug groups (80μmol/L methotrexate). Conclusion: Hence, β-sitosterol could contribute to the inhibition of RA by modulating cell proliferation and regulating the aforementioned six core proteins, potentially through the regulation of the FoxO and PI3K/AKT signaling pathways.

Therapeutic effects and mechanisms of berberine on enteritis caused by Salmonella in poultry.

The present study aimed to investigate the therapeutic effects of berberine (BBR) on Salmonella enteritis in broiler chickens and to elucidate its mechanisms of action preliminarily. Blood samples were collected from 21- to 35-day-old Sanhuang male chicks to measure immune and biochemical indicators and to calculate the organ coefficients for the liver, spleen, bursa of Fabricius, and thymus. The caecal microbiota was analysed through 16S ribosomal RNA (rRNA) gene sequencing, and transcriptome sequencing was conducted. Compared with the positive control group (S), the berberine-treated group (BS) presented increased serum immunoglobulin M (IgM) levels, serum IgG levels, and total antioxidant capacity; berberine ameliorated the increase in the thymus index caused by Salmonella administration. The addition of berberine to the diet increased the abundance of beneficial bacterial genera, including Bacteroides and Lactobacillus. It also decreased the abundance of harmful bacterial genera, including Faecalibacterium and Streptococcus. Transcriptome analysis revealed that gene expression in the S and BS groups was associated with T cell selection and B cell receptor signalling pathways, which are enriched primarily in multiple immune-related signalling pathways, including the B cell receptor signalling pathway, NF-κ B signalling pathway, intestinal immune network for IgA production, asthma, and African trypanosomiasis. The significantly expressed genes included ATAD5, ERP29, MGST2, PIK3CA, and HSP90AA1. The present study demonstrated that berberine has a good therapeutic effect on Salmonella infection in chicks, as it inhibits the occurrence and development of Salmonella-induced intestinal inflammation by regulating the balance of the gut microbiota and the expression of related genes, including ATAD5, ERP29, MGST2, PIK3CA, and HSP90AA1.

Decoding the anti-hypertensive mechanism of α-mangostin based on network pharmacology, molecular docking and experimental validation.

Hypertension is a leading risk factor for disability and deaths worldwide. Evidence indicates that alpha-mangostin(α-MG) can reduce blood pressure and improve target organ damage. Nonetheless, its pharmacological targets and potential mechanisms of action remain inadequately elucidated. We used SwissTargetPrediction to identify α-MG's drug targets and DisGeNET, GeneCards, CTD, and GEO databases for hypertension-related targets, and then determined antihypertensive therapeutic targets of α-MG by intersecting these targets. GO functional enrichment analysis, KEGG pathway analysis, and disease association analysis were conducted using the DAVID database and R package "clusterprofile", visualized with Cytoscape software. The binding affinity of α-MG to identified targets was confirmed through molecular docking using Autodock Vina v.1.2.2 software. The impact of α-MG on target genes was validated using an Angiotensin II-induced hypertensive mouse model and RT-qPCR. A total of 51 potential antihypertensive therapeutic targets for α-MG were identified by intersecting 109 drug targets with 821 disease targets. Furthermore, 10 cellular component terms, 10 disease terms, and the top 20 enriched biological processes, molecular functions, and KEGG pathways related to α-MG's antihypertensive effects were documented. Molecular docking studies indicated a strong binding affinity of α-MG with the HSP90AA1 domain. In Ang II-induced hypertensive mice aorta, treatment with α-MG effectively reversed the aberrant mRNA expression of TNF, HSP90AA1, NFKB1, PPARG, SIRT1, PTGS2, and RELA. Our analyses showed that TNF, HSP90AA1, NFKB1, PPARG, SIRT1, PTGS2, and RELA might be α-MG's potential therapeutic targets for hypertension, laying groundwork for further investigation into its pharmacological mechanisms and clinical uses.

Overcoming Stress Response-Induced Drug Resistance through Targeting CDK9 in Ph+ Leukemia

Overcoming Stress Response-Induced Drug Resistance through Targeting CDK9 in Ph+ Leukemia

Blestriarene C exerts an inhibitory effect on triple-negative breast cancer through multiple signaling pathways.

Breast cancer is the most common cancer worldwide, the leading cause of cancer death in women, and the fifth leading cause of cancer death. Triple negative breast cancer (TNBC), with high metastasis and mortality rates, is the most challenging subtype in breast cancer treatment. There is an urgent need to develop anti-TNBC drugs with significant efficacy, low side effects and good availability. In early drug screening, blestriarene C was found to have inhibitory effects on TNBC cells. In this article, we further explore the mechanisms associated with blestriarene C for breast cancer. In this article, we take the approach of network pharmacology combined with in vivo and in vitro experiments. Network pharmacology analysis was used to predict the active components in Baiji, and to investigate the hub targets and related mechanisms of BC in TNBC treatment. The mechanism of anti-TNBC in vitro was evaluated by CCK-8 assay, cell apoptosis and cell cycle assays, wound healing assay, WB assay, and molecular docking analysis. The inhibition effect in vivo was test in subcutaneous tumor models established in mice. Through network pharmacology analysis and experiments, we screened out BC as the main active ingredient, and found that BC could inhibit the Ras/ERK/c-Fos signaling pathway while downregulating the expression of HSP90AA1 and upregulating the expression of PTGS2, thereby promoting apoptosis, causing S-phase cycle arrest, and inhibiting the proliferation and migration of BT549 cells. The in vivo results illustrated that BC inhibited the growth of TNBC tumors and has a high safety profile. By integrating network pharmacology with in vitro and in vivo experiments, this study demonstrated that BC inhibited the proliferation and migration of TNBC cells by inhibiting the Ras/ERK/c-Fos signaling pathway, promoting apoptosis, and causing S-phase cycle arrest. This study provides new evidence for the use of BC as a novel drug for TNBC treatment.

Targeting telomerase with MST-312 leads to downregulation of CCND1, MDM2, MYC, and HSP90AA1 and induce apoptosis in Jurkat cell line.

Acute lymphoblastic leukemia is a challenging disease to treat, especially in older adults who are most commonly diagnosed and have a high risk of relapse, even with current treatment options. MST-312, targets the RNA component of telomerase, inhibiting its activity and leading to growth arrest and telomere shortening in cancer cells. This study aimed to investigate the effects of MST-312 on apoptosis rates and the expression of telomerase target genes, CCND1, MDM2, MYC, and HSP90AA1, in Jurkat cell line. Jurkat cell line was cultured and treated with various concentrations of MST-312(0 µM, 0.5 µM, 1 µM, 2 µM, and 4 µM). The optimal concentration of MST-312 was determined using MTT assay. Flow cytometry was employed to evaluate the apoptosis induced by MST-312 treatment. The expression levels of the target genes were measured using real-time polymerase chain reaction before and after the treatment with MST-312. P-value < 0.05 was considered statistically significant. The percentages of apoptotic cells after 48 h, as determined by flow cytometry analysis, were 30.32%, 52.35%, 57.60%, and 68.82%, respectively, compared to the control group which was 4.6%. The expression levels of all genes, including CCND1, MDM2, MYC, and HSP90AA1, were decreased compared to the control group. The results showed that MST-312 induced dose- and time-dependent apoptosis and downregulated the expression of CCND1, MDM2, MYC, and HSP90AA1in Jurkat cell line.