Search Results (917)

Sarcopenia, an age-related muscle atrophy disease, is a major health concern in aging societies and is closely associated with severe chronic diseases. Its primary pathogenesis involves oxidative stress-induced apoptosis in muscle cells and an imbalance in protein metabolism. This study evaluated the potential of Rhododendron mucronulatum branch extract (RMB) and its major flavonoids, taxifolin-3-O-arabinopyranoside (Tax-G) and taxifolin (Tax-A), as natural therapeutic agents for sarcopenia. Phytochemical analyses were performed using TLC, HPLC, LC-MS/MS, and NMR, and Tax-G and Tax-A were isolated from RMB. In vitro models of apoptosis and muscle atrophy were established in C2C12 cells using H₂O₂ and dexamethasone (DEX), respectively. Cell viability, myotube diameter, and protein expression related to apoptosis and muscle differentiation were assessed. All three substances reduced H₂O₂-induced apoptosis by increasing Bcl-2 and inhibiting cleaved caspase-3 and PARP. They also attenuated DEX-induced muscle atrophy by suppressing Atrogin-1, MuRF1, and FoxO3α while promoting MyoD, Myogenin, Akt, and mTOR. Although Tax-A showed the highest activity, Tax-G exhibited comparable effects with lower cytotoxicity. These findings demonstrate that RMB and its active compounds protect muscle cells by regulating apoptosis and muscle metabolism, suggesting their potential as safe and functional natural materials for the prevention of sarcopenia. Full article

Objective: β-cell dysfunction and loss are major pathological determinants of impaired islet function and hyperglycemia in diabetes. Given the inability of current therapies to restore β-cell viability or glucose-responsive insulin secretion, this study aimed to investigate whether a cell-permeable PBX1 fusion protein (TAT-PBX1) could rescue streptozotocin (STZ)-induced β-cell injury and restore β-cell functional integrity. Methods: A TAT-PBX1 recombinant fusion protein was produced using a prokaryotic expression system. Its protective effects were assessed in STZ-treated MIN6 β cells and in a mouse model of STZ-induced diabetes, with the glucokinase (GK) activator dorzagliatin included as a positive control. We evaluated β-cell apoptosis, DNA damage, ATP and NAD⁺/NADH levels, insulin signaling (IRS1/PI3K/Akt), and the expression of PDX1 and GK. Glucose-stimulated insulin secretion (GSIS), glucose tolerance, islet morphology, and β-cell proliferation were also examined in vivo. Results: TAT-PBX1 was detectable and significantly enriched in pancreatic tissue and mitigated STZ-induced cytotoxicity by reducing DNA damage, PARP1-associated energy depletion, and β-cell apoptosis. It restored intracellular ATP and NAD⁺/NADH ratios and reactivated IRS1/PI3K/Akt signaling. TAT-PBX1 further enhanced PDX1 protein levels and upregulated GK, resulting in improved glucose uptake and GSIS. In addition, it increased Ki67⁺ β-cell proliferation. In diabetic mice, TAT-PBX1 improved glucose tolerance, preserved islet morphology and number, and improved insulin signaling responsiveness. Conclusions: TAT-PBX1 restores β-cell function through coordinated protection of cellular metabolism and insulin signaling, leading to improved β-cell survival, glucose responsiveness, and regenerative capacity. These findings support TAT-PBX1 as a promising molecular strategy for β-cell-protective and β-cell-restorative diabetes therapy. Full article

Ovarian cancer (OC) remains one of the most lethal gynecologic malignancies due to late diagnosis, rapid progression, and frequent chemoresistance. Despite advances in targeted therapy, durable responses are uncommon, underscoring the need for novel multitarget agents capable of modulating key oncogenic networks. Medicarpin, a natural pterocarpan phytoalexin, exhibits diverse pharmacological activities; however, its molecular mechanisms in OC are poorly defined. This study employed an integrative in silico framework combining network pharmacology, pathway enrichment, molecular docking, and survival analysis to elucidate medicarpin’s therapeutic landscape in OC. A total of 107 overlapping targets were identified, resulting in a dense protein–protein interaction network enriched in kinase-mediated and apoptotic signaling pathways. Ten hub genes were emphasized: CASP3, ESR1, mTOR, PIK3CA, CCND1, GSK3B, CDK4, PARP1, CHEK1, and ABL1. Gene Ontology and KEGG analyses demonstrated substantial enrichment in the PI3K–Akt/mTOR and prolactin signaling pathways. Docking revealed the stable binding of medicarpin to CASP3 (−6.13 kcal/mol) and ESR1 (−7.68 kcal/mol), supporting its dual regulation of hormonal and apoptotic processes. Although CASP3 and ESR1 expression alone lacked prognostic significance, their network interplay suggests synergistic relevance. Medicarpin exhibits multitarget anticancer potential in OC by modulating kinase-driven and hormone-dependent pathways, warranting further experimental validation. Full article

Background: Breast cancer remains the most common malignancy among women worldwide. Current systemic treatment strategies include chemotherapy, immunotherapy, bone-stabilizing agents, endocrine therapy for hormone receptor-positive disease, anti-HER2 therapy for HER2-positive disease, and poly (ADP-ribose) polymerase (PARP) inhibitors for BRCA mutation cases. However, effectively overcoming drug resistance and reducing recurrence and metastasis rates remain major therapeutic challenges. Methods: To investigate the underlying mechanism of RSL3 in PARPi-resistant breast cancer cells, we treated several PARPi-resistant breast cancer cells with varying doses of RSL3. The regulatory proteins of STAT3 were analyzed using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. Immunoprecipitation and ubiquitination assay were performed to identify the STAT3 ubiquitination levels. Results: Recently, we identified that RSL3, a ferroptosis activator, exhibits potent antitumor activity against PARPi-resistant breast cancer. Yet, its underlying mechanism remains unclear. Here, we demonstrate that RSL3 directly targets STAT3 and promotes its degradation via the ubiquitination pathway, leading to increased LC3-II levels and decreased p62 expression. These changes ultimately enhance autophagy, which at least partially contributes to elevated apoptosis. Rescue experiments confirmed that STAT3 overexpression reverses RSL3-induced autophagy and apoptosis. Conclusions: Our findings highlight RSL3 as a promising therapeutic agent and STAT3 as a potential target for treating PARPi-resistant breast cancer. Full article

The substantial interest in plant-based drugs or plant-derived phytocompounds drives researchers to conduct comprehensive investigations on their therapeutic properties. Mollugin, one of the major active constituents of Rubia cardifolia, has been well-studied for its pharmacological properties, demonstrating potent anti-inflammatory properties by suppressing the TAK-1-mediated activation of NF-κB/MAPK and enhancing the Nrf2/HO-1-mediated antioxidant response. It exhibits strong anticancer effects through ferroptosis via IGF2BP3/GPX4 pathways, induces mitochondrial apoptosis, and targets NF-κB, ERK, and PI3K/Akt/mTOR to suppress tumor progression. Mollugin also inhibits JAK2/STAT and PARP1 pathways, suppressing IL-1β expression via the modulation of ZFP91. Moreover, it regulates the MAPK/p38 pathway, promotes neuroprotection, and improves cognitive performance through GLP-1 receptor activation. Mollugin promotes osteogenesis by activating the BMP-2/Smad1/5/8 signaling pathway and downregulates MAPK, Akt, and GSK3β expression, leading to the inhibition of osteoclastogenesis. It overcomes multidrug resistance by downregulating MDR1/P-gp, CREB, NF-κB, and COX-2 through AMPK activation. Its antibacterial effect is mediated by strong binding to FUR, UDP, and IpxB proteins in Enterobacter xiangfangensis. Mollugin mitigates Klebsiella pneumoniae infection, suppresses adipogenesis without causing cytotoxicity, and protects endothelial cells via the BDNF/TrkB-Akt signaling pathway. Synthetic derivatives of mollugin, such as oxomollugin and azamollugin, have shown enhanced anticancer and anti-inflammatory effects by regulating EGFR, PKM2, TLR4/MyD88/IRAK/TRAF6, and NF-κB/IRF3 pathways with improved solubility and stability. Collectively, these findings emphasize the broad-spectrum activity of mollugin. This review provides a critical interpretation of the mechanistic pathways regulated by mollugin and its derivatives, emphasizing their pharmacological significance and exploring their potential for future translation as multitarget drug candidates. Full article

Background: Biliary tract cancer (BTC) is an aggressive malignancy with poor prognosis and limited therapeutic options. Poly(ADP-ribose) polymerase (PARP) inhibitors have demonstrated efficacy in tumors with homologous recombination repair (HRR) deficiency. However, actionable BRCA1/2 mutations are rare in BTC. Epigenetic modulation via DNA methyltransferase (DNMT) inhibition is a proposed strategy for inducing an HR-deficient (“BRCAness”) phenotype and thereby enhancing therapeutic response to PARP inhibitors. This study aimed to determine whether the DNMT inhibitor azacitidine (AZA) enhances the antitumor effects of the PARP inhibitor niraparib (NIR) and to identify molecular mechanisms underlying this interaction. Methods: Two BTC cell lines, TFK-1 and RBE, were treated with AZA and/or NIR or subjected to siRNA-mediated DNMT1, DNMT3A, or DNMT3B knockdown. Functional analyses included homologous recombination (HR) assays, flow cytometric evaluation of cell-cycle distribution and apoptosis, proliferation and survival assays, and IC₅₀ determination. Whole-transcriptome RNA sequencing was performed to identify differentially expressed genes after AZA treatment or DNMT3B knockdown, followed by validation via qPCR and Western blotting. To explore epigenetic regulation, whole-genome bisulfite sequencing was performed on TFK-1 cells following DNMT3B knockdown. Results: AZA treatment decreased HR frequency in a dose-dependent manner and enhanced the sensitivity of BTC cells to NIR, as evidenced by increased apoptosis, suppressed proliferation, and reduced IC₅₀ values. DNMT3B knockdown recapitulated these effects, establishing a causal relationship between DNMT3B suppression and disrupted HR repair. RNA sequencing identified opioid growth factor receptor (OGFR) as a commonly upregulated gene after DNMT3B knockdown. Functional validation showed that OGFR overexpression reduced HR activity, increased apoptosis, and enhanced NIR sensitivity. Contrarily, OGFR knockdown conferred relative resistance. Whole-genome bisulfite sequencing showed no significant CpG methylation changes at the OGFR promoter region, indicating that OGFR induction is mediated through DNMT3B-dependent transcriptional regulation rather than direct promoter demethylation. Conclusions: DNMT3B inhibition sensitizes BTC cells to PARP inhibitors by disrupting HR repair. OGFR was identified as a novel regulator of HR and PARP inhibitor sensitivity, controlled via noncanonical DNMT3B-dependent transcriptional mechanisms that operate independently of CpG methylation. These findings provide new mechanistic insights into the epigenetic control of DNA repair and support the rationale for combining DNMT and PARP inhibitors as a promising therapeutic strategy for BTC beyond genetically HR-deficient cases. Full article

Small-cell lung carcinoma (SCLC) is one of the most aggressive and therapeutically challenging malignancies. It is characterised by rapid progression, early metastasis and frequent relapse. Despite considerable advances in molecular oncology, effective biomarkers for prognosis and treatment response remain elusive. In this review, we summarise and discuss recent evidence on microRNAs (miRNAs) as central regulators of SCLC biology and their potential clinical applications. A narrative review of the literature was conducted. Search of PubMed and Scopus databases identified 14 miRNAs, including miR-7-5p, miR-22-3p, miR-134, miR-181b, miR-200b, miR-335, miR-335-5p, miR-495, miR-24-3p, miR-30a-5p, miR-30a-3p, miR-100, miR-1 and miR-494, which are linked to tumour progression, therapy resistance and metastasis. These molecules influence several signalling cascades, including PI3K/Akt, Hippo, TGF-β, PARP1-mediated DNA repair and autophagy. Their abnormal expression correlates with patient outcome and may enable plasma- or exosome-based non-invasive monitoring. In particular, strategies that restore or inhibit miRNA activity using mimics or antagomiRs show promise in improving drug sensitivity and complementing current treatment options. Overall, emerging evidence supports the integration of miRNA profiling into precision oncology for SCLC, with the aim of refining diagnosis, risk assessment and therapeutic decision-making. Full article

Oral squamous cell carcinoma (OSCC) is an aggressive malignancy characterized by high invasiveness and poor prognosis. This study investigated the anticancer mechanisms of eupatilin, a pharmacologically active flavonoid derived from Artemisia species, in human OSCC YD-10B cells. Eupatilin significantly reduced cell viability in a dose-dependent manner, with an IC₅₀ of approximately 50 μM. Flow cytometric analysis revealed G0/G1 phase arrest accompanied by downregulation of Cyclin D1 and CDK2, and upregulation of p21. Annexin V/Propidium Iodide staining and Western blotting confirmed apoptosis induction through activation of Bax, cleaved caspase-3/9, and poly ADP-ribose polymerase (PARP) cleavage, alongside suppression of Bcl-2. Furthermore, eupatilin markedly decreased both the mRNA expression and enzymatic activities of matrix metalloproteinases (MMP)-2 and MMP-9, indicating its potential to inhibit cancer cell invasion. Collectively, these findings demonstrate that eupatilin exerts potent antiproliferative and anti-invasive effects on OSCC cells via cell-cycle modulation and mitochondrial-mediated apoptosis. This study provides the first evidence of eupatilin’s therapeutic potential against OSCC, suggesting its promise as a natural compound for the development of safer and more effective treatments for oral cancer. Full article

Ovarian cancer stem cells (OCSCs) possess stemness; differentiation capacity; and tolerance to oxidative, metabolic, and therapeutic stress, driving recurrence and chemoresistance. Emerging evidence highlights a synergistic interplay between redox homeostasis and amino acid metabolism in maintaining stemness and treatment resistance. This review integrates redox regulation, amino acid metabolic reprogramming, and tumor microenvironment (TME) signals into a unified “redox–amino acid–TME” framework. OCSCs balance signal transduction and antioxidant defense by fine-tuning reactive oxygen species (ROS) levels. Glutamine, serine/glycine, and sulfur amino acid metabolism collectively generate NADPH and glutathione, sustaining the GPX4/TRX antioxidant systems and suppressing ferroptosis. Branched-chain amino acid (BCAA)–mTOR and tryptophan (Trp)–aryl hydrocarbon receptor (AhR) axes couple amino acid sensing to redox signaling, stabilizing the stem-like phenotype. Under TME stress, including hypoxia, acidity, and nutrient competition, exosomes and stromal components reinforce stemness and immune evasion through metabolic and redox crosstalk. Therapeutically, targeting glutamine metabolism (ASCT2/GLS), serine biosynthesis (PHGDH/SHMT), or antioxidant defenses (xCT/GPX4) disrupts reducing power, increases oxidative stress, and enhances the efficacy of chemotherapy, PARP inhibition, and immunotherapy. Biomarkers such as xCT/GPX4 expression, PHGDH levels, Nrf2 activity, and GSH/NADPH ratios may guide patient stratification and response prediction. Overall, understanding the redox–amino acid metabolic network provides a mechanistic basis and translational opportunities for precision metabolic therapies in ovarian cancer. Full article

Metastatic or unresectable pheochromocytomas and paragangliomas (PPGLs) remain rare but clinically challenging neuroendocrine neoplasms with limited curative options. Traditionally managed with surgery, radionuclide therapy, or cytotoxic chemotherapy, systemic treatments have historically achieved disease stabilization, rather than durable remissions. In recent years, however, the therapeutic landscape has evolved substantially. Radiopharmaceuticals such as ¹³¹I-MIBG and ¹⁷⁷Lu-DOTATATE continue to play a pivotal role, achieving disease control in many patients. Cytotoxic regimens, particularly temozolomide, remain relevant, with some studies suggesting that SDHB-mutated PPGLs demonstrate a heightened sensitivity associated with MGMT promoter hypermethylation and reduced MGMT expression. Targeted agents are increasingly important: multi-kinase inhibitors such as sunitinib, anlotinib, and cabozantinib have shown meaningful activity. The landmark approval of belzutifan, a HIF-2α inhibitor, in 2025 represents the first oral targeted therapy for advanced/metastatic PPGL, which is particularly relevant for pseudohypoxic Cluster 1 tumors. Immunotherapy has yielded modest responses with checkpoint inhibitor monotherapy, but ongoing studies of dual checkpoint blockade and TKI–ICI combinations hold promise. Novel approaches, including PARP inhibition, metabolic targeting strategies, and cancer vaccines, are under investigation, especially for aggressive SDHB-related disease. Optimal sequencing of these therapies is emerging as a central challenge, with treatment strategies increasingly tailored to molecular genotype, tumor behavior, and functional imaging phenotype. This review summarizes current evidence and highlights ongoing clinical trials, underscoring a paradigm shift toward precision medicine and rational combination strategies. Collectively, these advances bring cautious optimism that metastatic PPGLs may soon become a more manageable chronic disease with improved survival and quality of life. Full article

Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease whose molecular mechanisms of action remain incompletely characterized. This study was designed to develop potential diagnostic biomarkers and unravel the pathogenic causes of UC activity through the integration of transcriptome analysis with machine learning and genetic causal inference. Methods: Gene expression datasets (GSE75214, GSE53306, GSE179285) from the GEO database were evaluated. Weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) analysis were applied to discover activity-associated genes. Protein–protein interaction networks and ensemble machine learning methods were utilized to refine the potential list. Furthermore, summary-data-based Mendelian Randomization (SMR) analysis and immune infiltration research were conducted. Results: Eight characteristic genes were identified, with CXCL11, PARP14, and IFITM1 emerging as hub genes. These hub genes exhibited strong diagnostic accuracy, with consistent area under the curve (AUC) values exceeding 0.83 across 3 independent cohorts. SMR analysis demonstrated a probable causal connection between higher PARP14 and UC susceptibility. The hub genes were strongly correlated with immune cells, including M1 macrophages and NK cells. FLI1 was discovered as a critical upstream transcription factor regulating this network. Conclusions: The findings outline a FLI1-PARP14-immune axis central to UC activity, providing unique insights into its pathophysiology and highlighting PARP14 as a promising diagnostic biomarker and potential therapeutic target. Full article

Background/Objectives: Honokiol (HK), a bioactive phenolic compound, exhibits significant anti-cancer properties. This study aimed to investigate the anti-cancer effects of HK in colorectal cancer (CRC) cells by focusing on its direct interaction with heat shock protein 27 (Hsp27) as a molecular target, and to elucidate the underlying mechanisms involved. Methods: HK was isolated via silica/ODS chromatography. Anchorage-independent growth of CRC cells was quantified using a soft agar assay with increasing HK concentrations. Apoptosis and cell cycle were analyzed by flow cytometry, and cell viability by MTS assay. Hsp27 binding to HK was validated by pull-down assay with HK-conjugated Sepharose 4B beads. Hsp27 knockdown was performed using lentiviral shRNA in CRC cells. Molecular docking of HK-Hsp27 interaction employed Schrödinger Suite 2016. Protein expressions, including chaperone and apoptotic proteins, were evaluated by Western blotting. Results: HK dose-dependently suppressed anchorage-independent growth of CRC cells and induced G₀/G₁ arrest. It triggered apoptosis through cytochrome c release, PARP cleavage, and Bcl-2 downregulation. HK directly bound to the α-crystallin domain of Hsp27 at Asn102 and His103 residues, confirmed by computational molecular docking and site-directed mutagenesis. Hsp27 knockdown in CRC cells dramatically reduced anchorage-independent growth. HK markedly decreased Hsp27 protein levels while having less effect on other heat shock proteins in CRC cells. Conclusions: HK exerts anti-cancer effects in CRC cells, associated with Hsp27 inhibition, resulting in suppressed cell growth and increased apoptosis. This interaction between HK and Hsp27 may support a mechanistic foundation supporting the potential utility of HK as a natural therapeutic agent for CRC. Full article

Breast cancer remains a leading cause of mortality among women despite advances in early detection and targeted therapies, underscoring the need for safer and more effective treatment options. Drug repurposing offers a promising strategy by leveraging existing pharmacological agents with established safety profiles. Desloratadine, a second-generation H1-histamine receptor antagonist widely prescribed for allergic conditions, has attracted interest in oncology because histamine signaling influences proliferation, angiogenesis, and immune responses, yet its anticancer potential remains poorly understood. In this study, we investigated its effects in MCF-7 breast cancer cells, which harbor wild-type TP53. Desloratadine inhibited cell viability in a dose-dependent manner, with an IC₅₀ of 14.2 µg/mL. Mechanistic analyses revealed that growth inhibition was primarily mediated through apoptosis, confirmed by Hoechst 33342 staining, ROS generation, annexin V/PI staining, and caspase-dependent pathways. Gene expression profiling demonstrated upregulation of TP53, FAS, and BAX, alongside reduced PARP-1 and NF-κB expression, with no detectable STAT3 or BCL2 expression. Flow cytometry indicated accumulation of cells in the sub-G₁ phase and G₂/M arrest, consistent with apoptosis induction. Molecular docking further supported these findings, showing that Desloratadine binds with high affinity to p53 (−7.0 kcal/mol), FAS (−6.8 kcal/mol), and NF-κB (−6.5 kcal/mol), forming stabilizing hydrogen bonds and hydrophobic interactions aligned with the observed gene expression changes. To confirm the functional role of TP53, we generated CRISPR-Cas9 knockout MCF-7 cells. Compared with wild-type cells, these knockout cells displayed markedly reduced sensitivity to Desloratadine, with the IC₅₀ shifting from 14.2 µg/mL to 36.4 µg/mL, demonstrating that p53 is a key mediator of the drug’s cytotoxic effect. Collectively, these findings identify Desloratadine as a potential repurposed drug candidate for breast cancer therapy, acting at least in part through a p53-dependent apoptotic pathway. Full article

Cervical cancer ranks as a primary contributor to cancer-related deaths in women globally and is the fourth most prevalent malignant neoplasm. Cepharanthine, a naturally occurring biscoclaurine alkaloid extracted from Stephania cepharantha, has demonstrated anticancer and antimetastatic efficacy across multiple cancer types. However, its mechanism of action in cervical cancer remains unexplored. Our results demonstrated that cepharanthine effectively suppressed the proliferation and motility of the CaSki, HeLa, and C33A cell lines. Furthermore, cepharanthine triggered apoptosis through Bcl-2 suppression and increased cleaved-PARP-1, Bax, and cleaved-caspase-3 expression and AMPK/p53 phosphorylation, while inducing G0/G1 phase arrest in CaSki cells and sub-G1 phase arrest in HeLa and C33A cells. Additionally, cepharanthine reduced the mitochondrial membrane potential (∆ψm), compromised mitochondrial functionality, and increased reactive oxygen species (ROS) accumulation, promoting oxidative stress via the modulation of the Nrf2/Keap1 pathway in CaSki, HeLa, and C33A cells, which exhibit an anti-cervical cancer effect. Similarly, cepharanthine markedly reduced tumor progression in C33A BALB/c nude mice, which aligns with the in vitro observations. Collectively, these findings indicate that cepharanthine has potential therapeutic applications in the treatment of cervical cancer and warrants future clinical investigation. Full article

To date, breast cancer remains one of the leading causes of death among women worldwide. Although various treatments are used in clinical settings, the efficacy and safety of such treatments are limited by tumor biology factors and patient preferences. Previous studies have shown that triple-negative BRCA1-deficient breast cancer is susceptible to DNA-damaging agents, including platinum-based drugs and poly(ADP-ribose) polymerase (PARP) inhibitors, alone or in combination. To address whether the combinative treatment of these DNA-damaging agents can be extended to the triple-negative BRCA1-proficient breast cancer population, we investigated the anticancer activity of the well-known FDA-approved PARP inhibitor olaparib in combination with the antimetastatic ruthenium(II)–arene PTA compound RAPTA-T for triple-negative BRCA1-competent breast cancer cells (MDA-MB-468 and MDA-MB-231), with consideration of sporadic breast cancer MCF-7 cells. RAPTA-T, olaparib, and the combined agents exhibited a dose-dependent inhibition of breast cancer cell growth in selected breast cancer cells. The combination compound inhibited colony formation most effectively in MDA-MB-468 cells. Additionally, the scratch-wound assay showed that MDA-MB-468 cells migrated more slowly than MCF-7 and MDA-MB-231 cells. The results indicated that the olaparib and RAPTA-T combination can reduce or inhibit the survival, invasion, and metastasis of breast cancer cells. Moreover, the combined agents promoted apoptotic cell death, with a higher percentage of apoptosis observed in MDA-MB-468 cells than in MDA-MB-231 and MCF-7 cells. Olaparib and RAPTA-T also interfered with cell cycle progression, with the greatest inhibition observed in the S and G2/M phases of MCF-7 cells (1.6- and 3.4-fold), followed by MDA-MB-468 cells (1.6- and 1.8-fold) and MDA-MB-231 cells (1.5- and 1.4-fold). Interestingly, MDA-MB-468 cells presented the highest degree of inhibition for BRCA1 replication and BRCA1 expression. The p53, PARP, and Chk1 proteins were more strongly upregulated in MDA-MB-231 cells than in Ru-untreated control cells. Moreover, the expression levels of protein biomarkers associated with the epithelial-to-mesenchymal transition (EMT), including E-cadherin and SLUG, were remarkably reduced in all tested breast cancer cells. Together, our results show the feasibility of extending the application of PARP inhibitors beyond breast cancer with BRCA1 mutations and optimizing the combinative treatment of PARP inhibitors with antimetastasis ruthenium-based chemotherapy as new therapeutic approaches for TNBC harboring wild-type BRCA1. Full article