Background/Objectives: Cancer is the second leading cause of death globally. Medicinal plants have emerged as fundamental sources of bioactive compounds with anticancer potential, largely attributed to their diverse secondary metabolites. This study aimed to investigate the cytotoxic effects of Helichrysum arenarium extracts from two distinct regions of Turkiye, Mersin, and Artvin, on cancerous (MDA-MB-231, RT4, T98G) and non-cancerous (ARPE-19, hGF) cell lines and to identify bioactive compounds responsible for these effects. Methods: H. arenarium plant extracts were prepared using ethanol and methanol as solvents, followed by lyophilization and dissolution in DMSO. The cytotoxic effects of the extracts were evaluated using Hoechst staining and MTS assays to assess cell viability. IC50 values and selectivity indices were calculated. Phytochemical composition was analyzed using Quadrupole Time-of-Flight mass spectrometry. Results: The ethanol extract from Mersin (HAE-M) demonstrated superior cytotoxicity, particularly against breast and bladder cancer cells, while showing minimal impact on non-cancerous cells. HAM-M, HAE-A, and HAM-A exhibited comparatively less potent effects. Phytochemical analysis of HAE-M identified 16 bioactive compounds, including Naringenin, Luteolin, and Quercitrin, known for their antioxidant and anticancer properties. Conclusions: These findings highlight the potential of H. arenarium extracts, particularly HAE-M, as a source of potent anticancer agents. This study is novel in its comprehensive analysis of different extraction methods and regional plant sources, combined with phytochemical profiling, to identify selective anticancer effects. Further investigations into the mechanisms of action of these extracts could contribute to the development of plant-derived anticancer therapies.

Background: Acute myeloid leukemia (AML) is a malignancy characterized by the clonal expansion of hematopoietic stem and progenitor cells, often associated with mutations such as NPM1. DOT1L inhibitors have shown potential as new therapeutic opportunities for NPM1-mutant AML. The aim of this study was to investigate potential alternative targets of the small-molecule inhibitor EPZ004777, in addition to its primary target, DOT1L, using RNA sequencing data from the NCBI-GEO database (GSE85107). Methods: Differentially expressed genes (DEGs) were identified through bioinformatic analysis, followed by pathway enrichment analysis to uncover the relevant biological pathways. Additionally, molecular docking analysis was conducted to assess the binding affinity of EPZ004777 with the proteins CT45A3, HOXA4, SNX19, TPBG, and ZNF185, which were identified as significantly DEGs. The protein structures were obtained from AlphaFold and the Protein Data Bank. Results: EPZ004777 significantly altered gene expression. Oncofetal genes (CT45A3, TPBG) and genes associated with oncogenic pathways (HOXA4, ZNF185, SNX19) were downregulated, while the pro-apoptotic gene BEX3 was upregulated. Pathway enrichment analysis revealed the suppression of the Rap1 signaling pathway and cell adhesion molecules, which may reduce the invasiveness of AML cells. Additionally, upregulation of immune-related pathways suggests enhanced anti-tumor immune responses. Molecular docking analysis demonstrated that EPZ004777 has strong binding potential with SNX19, TPBG, and ZNF185 proteins. Conclusions: EPZ004777 has been identified as a potent modulator of SNX19, TPBG, and ZNF185 associated with apoptosis and tumor progression in AML.

Background/Objectives: Lavandula stoechas has reported bioactivities, but its selective anticancer potential in human models remains insufficiently defined. This study aimed to compare cytotoxicity and selectivity of ethanol and methanol extracts prepared from fresh and dried L. stoechas and to profile candidate bioactive metabolites. Methods: Aerial parts Lavandula stoechas L. subsp. stoechas (L. stoechas L.) were extracted with ethanol or methanol from fresh (LsFE, LsFM) and dried (LsDE, LsDM) material. Cytotoxicity was assessed in cancer (MDA-MB-231, T98G, RT4) and non-malignant (hGF, ARPE-19) cells using Hoechst 33342-stained nuclear counts and MTS viability at 24–48 h. Metabolite identification was performed using LC–QTOF–MS in both positive and negative ESI modes, supported by database search results. Results: All extracts reduced viability in a dose- and time-dependent manner. Among them, the ethanol extract from fresh material (LsFE) displayed the highest cytotoxic potency and the most favorable selectivity profile, markedly reducing viability in breast (MDA-MB-231) and glioblastoma (T98G) cells while exerting only mild effects on non-malignant fibroblast (hGF) and retinal epithelial (ARPE-19) cells. In contrast, extracts from dried material, particularly LsDE, showed broader cytotoxicity across both cancerous and non-cancerous lines. LC–MS highlighted sesquiterpenoids (Kikkanol A; 3(4→5)-Abeo-4,11:4,12-diepoxy-3-eudesmanol), phenolics (tyrosol; 3,4-dihydroxybenzoic acid), flavonoid/ionone derivatives (luteolin 5,3′-dimethyl ether; 3-hydroxy-β-ionone), oxidized fatty acids (9(S)-HpODE, α-EpODE, 5,12-dihydroxy-eicosatetraenoic acid), and jasmonates (12-hydroxyjasmonic acid; dihydrojasmonic acid methyl ester), especially enriched in LsFE. Conclusions: Ethanol extracts of L. stoechas L., especially LsFE, demonstrated selective cytotoxicity against cancer cells while exerting relatively mild effects on non-malignant cells. The metabolite profile of L. stoechas L. extracts revealed a diverse composition, including phenolics, terpenoids, flavonoids, and oxidized lipids, which are commonly associated with biological activity. These results suggest that LsFE is a promising candidate for further studies focusing on compound isolation and mechanistic analysis.

Bladder cancer, the fourth most common cancer type among men, remains a therapeutic challenge due to its heterogeneity and frequent development of chemoresistance. Cisplatin-based chemotherapy, often combined with gemcitabine, is the standard treatment, yet resistance and off-target effects in non-cancerous tissues limit its efficacy. This study evaluated the effects of cisplatin, gemcitabine, and the APC/C inhibitor proTAME, both individually and in combination, on cell migration and MMP2/MMP9 expression in RT4 bladder cancer and ARPE-19 normal epithelial cells. Molecular docking analyses were conducted to investigate the interactions of these compounds with MMP2 and MMP9. IC20 values for gemcitabine, cisplatin, and proTAME were applied in scratch-wound healing and quantitative real-time PCR (qRT-PCR) assays. Docking results predicted that proTAME may interact favorably with MMP2 (−9.2 kcal/mol) and MMP9 (−8.7 kcal/mol), showing high computational binding affinities and potential key hydrogen bonds; however, these interactions require further experimental validation. Scratch-wound healing and qRT-PCR assays demonstrated that proTAME-containing combinations were associated with reduced cell migration and decreased MMP2 and MMP9 expression in RT4 cells. Cisplatin combined with proTAME showed the most pronounced reduction in MMP expression and cell migration, with proTAME alone also exhibiting notable inhibitory effects. In ARPE-19 cells, gemcitabine and cisplatin upregulated MMP2 and MMP9 expression, suggesting a potential stress response, whereas proTAME mitigated this effect. These differential effects show the importance of tumor-specific responses in RT4 cells, where proTAME shows promise in enhancing the efficacy of chemotherapy by modulating MMP-related pathways involved in tumor migration and invasion. In conclusion, this study highlights the potential of proTAME as a repurposed agent in bladder cancer treatment due to its association with reduced cell migration and MMP downregulation. While these in vitro and in silico findings suggest a promising role for proTAME in combination therapies, further validation in advanced preclinical models is necessary to assess its therapeutic applicability and safety.

Background: Bladder cancer (BC) is one of the ten most common cancers worldwide, with a high recurrence rate and significant variation in clinical outcomes based on tumor grade and stage. This study aimed to investigate the gene expression profiles at different cancer stages to assess their potential prognostic value. Methods: RNA was extracted from paraffin-embedded BC tissues and the gene expression levels of CDC20 and CCNB1 were analyzed using qRT-PCR. A total of 54 BC patient samples were included in the analysis and categorized into low-grade (LG) (n = 23) and high-grade (HG) (n = 31) tumors, as well as stages pTa, pT1, and pT2. Results: CDC20 gene expression was significantly higher in the HG group (mean fold-change: 16.1) compared to the LG group (mean fold-change: 10.54), indicating a significant association with tumor grade (p = 0.039). However, no significant differences were observed in CDC20 expression across the cancer stages. For CCNB1, while gene expression was significantly elevated in higher-stage tumors (pT2 vs. pTa; p = 0.038), no significant association was found between CCNB1 expression and tumor grade. Survival analysis revealed that increased CCNB1 expression and advanced cancer stage were associated with poorer overall survival, whereas no significant impact of CDC20 expression or tumor grade on survival was observed. Correlation analysis indicated a positive relationship between CDC20 expression and tumor grade (r = 0.284, p = 0.038) and between CCNB1 expression and tumor stage (r = 0.301, p = 0.027). Conclusions: Our findings suggest that CDC20 overexpression is linked to higher tumor grades, while CCNB1 overexpression is associated with more advanced cancer stages in BC. These results underscore the potential utility of CDC20 and CCNB1 as biomarkers for tumor prognosis and as therapeutic targets. Further studies with larger cohorts are needed to validate these findings and better understand the molecular mechanisms driving BC progression.