Purpose: Cannabidiol (CBD) is a primary bioactive, non-intoxicating cannabinoid found in the cannabis plant. Studies have shown that CBD causes anticancer activity by inhibiting the expression of growth factors and inducing apoptosis, leading to cell cycle arrest. In this study, we aimed to determine how CBD influences the expression of genes that affect cancer pathways in doxorubicin-sensitive (MCF-7) and doxorubicin-resistant (MCF-7/Adr) breast cancer cells. Materials and Methods: IC₅₀ concentrations of CBD in MCF-7 and MCF-7/Adr cell lines were determined by the MTT cell cytotoxicity assay. RNA isolation and subsequent cDNA synthesis were performed for qPCR experiments with the determined IC₅₀ values. The effects of CBD on the cell cycle and apoptosis were studied using flow cytometry. IC₅₀ values of CBD were determined in MCF-7 and MCF-7/Adr breast cancer cell lines at eight different concentrations and at three different incubation periods (24 h, 48 h, and 72 h) with different doses. RT-qPCR was used to investigate the molecular mechanisms underlying the expression of genes involved in cancer pathway analysis. Results: Treatment with CBD at concentrations of 17.57 μM (MCF-7) and 11.41 μM (MCF-7/Adr) for 48 h decreased colony formation, induced apoptosis, and inhibited cell invasion in both cell lines. In addition, we observed significant alterations of angiogenesis, apoptosis, cell cycle, cellular senescence, DNA damage and repair, epithelial-to-mesenchymal transition, hypoxia, metabolism, telomeres, and telomerase in both cell lines. Conclusions: Our research indicates that CBD could be an effective natural bioactive compound for breast cancer treatment, inhibiting tumor cell proliferation and inducing apoptosis.

Background: Heat shock protein 90 (HSP90) is a molecular chaperone that stabilizes numerous oncogenic proteins and supports tumor survival. Small molecules targeting HSP90 offer a novel approach to overcome drug resistance and immune suppression in breast cancer. Methods: A novel thiazolyl benzodiazepine (TB) containing a hydrazone moiety was evaluated in breast cancer cell lines (ER⁺ MCF-7, TNBC MDA-MB-231, and HER2⁺ SK-BR-3). Cytotoxicity was assessed using the CCK-8 assay, followed by PCR sequencing, flow cytometry, RT-qPCR, protein profiling, and HSP90 binding assays. Results: TB showed the strongest activity in MCF-7 cells (IC₅₀ = 7.21 µM) compared to MDA-MB-231 (IC₅₀ = 28.07 µM) and SK-BR-3 (IC₅₀ = 12.8 µM) cells. Mechanistic studies showed that TB binds to HSP90 (Kd = 3.10 µM), leading to disruption of the oncogenic signal. TB induced G2/M cell cycle arrest, promoted apoptosis via Bax and Caspase-3 activation, and suppressed cancer stem cell markers (NANOG, OCT4, SOX2). Additionally, TB activated immune-related pathways via ERK/MAPK signaling and upregulated genes such as SMAD2, SMAD3, and JUN.Conclusions: TB functions as an HSP90 inhibitor with dual anticancer and immunomodulatory properties in Estrogen Receptor-Positive (ER⁺) breast cancer cells. These findings suggest that TB represents a promising scaffold for the development of multi-targeted breast cancer therapies.

In this study, four stages were used to create brand-new p-tert-butyl-calix [4] arene Schiff base derivatives. First, p-tert-butyl-phenol and formaldehyde are reacted to create p-tert-butyl-calix [4] arene (1). In the following step, methyl bromoacetate and p-ter-butyl-calix [4] arene (1) were combined with acetone and reflux to create the p-tert-butyl-calix [4] arene diester complex (2). The third step involves reacting the diester compound (2) and hydrazine hydrate to create the p-tert-butyl-calix [4] arene hydrazinamide molecule (3). In the final stage, calix [4] arene Schiff base derivatives (4a-d) were produced in good yields by combining compound (3), p-tert-butyl-calix [4] arene hydrazinamide, and various aldehyde derivatives with reflux in EtOH. Through the use of 1H-NMR, 13C-NMR, infrared spectroscopy, and elemental analysis, the structures of produced compounds were verified. Four distinct cancer lines are linked to the antitumor activity of synthetic chemicals. (HT-29, a human colon cancer cell line, PC-3, a human prostate cancer cell line, C6, a rat glioma cell line and MCF-7, a human breast cancer cell line). Weak antitumor activity was seen in synthetic substances. However, only compound 4b was found to have potential efficacy against C6 and HT-29. It is clear that compound 4b, which has a nitro substitute on the phenyl ring, draws attention due to its increased activity.

Background: Cigarette smoking disrupts cellular energy metabolism and remains a major global health problem. The Mediterranean diet, characterized by antioxidant and anti-inflammatory properties, has been implicated in the regulation of metabolic pathways. Objective: This study aimed to examine the association between adherence to the Mediterranean diet and the expression of energy metabolism-related genes in smokers aged 18–55 years. Methods: Smokers were classified according to their Mediterranean Diet Adherence Screener (MEDAS) scores into an adhering group (n = 24) and a non-adhering group (n = 24). Participant characteristics were recorded, blood samples were collected, and total RNA was isolated. Gene expression analysis was performed using a custom RT-qPCR array targeting energy metabolism-related genes. Pathway enrichment analysis was conducted using EnrichR Reactome 2024, and gene–metabolite relationships were explored using MetaboAnalyst 6.0 to support pathway-level interpretation. Results: Smoking was associated with coordinated upregulation of genes involved in glycolysis, glucose transport, lipid metabolism, amino acid metabolism, the pentose phosphate pathway, and redox regulation, consistent with a metabolically stressed state. In contrast, adherence to the Mediterranean diet was associated with lower expression of genes related to glycolytic flux, lipid β-oxidation, and amino acid turnover, alongside relatively higher engagement of tricarboxylic acid cycle-related pathways and reduced activation of redox-associated processes. Conclusions: Adherence to the Mediterranean diet was associated with differences in the expression of genes involved in cellular energy metabolism among smokers, suggesting a potential modulatory role of dietary patterns in smoking-related metabolic alterations.

Introduction/Objective: Breast cancer is the most common malignancy among women worldwide, and the emergence of resistance to anthracycline-based chemotherapy remains a major clinical challenge. Benzimidazole scaffolds have attracted considerable interest in medicinal chemistry due to their broad pharmacological properties and anticancer potential. This study aimed to investigate the anticancer activity, selectivity, and molecular mechanisms of novel nitro-benzimidazole derivatives in luminal and Adriamycin-resistant breast cancer cell lines. Methods: A series of benzimidazole derivatives was synthesized and evaluated using in silico pharmacokinetic analyses. Cytotoxicity was assessed by MTT assay in MCF-7, adriamycinresistant MCF-7 (MCF-7/Adr), and normal human fibroblast cells CCD-1072sk. The most active compound was further investigated by RT-qPCR-based gene expression and pathway enrichment analyses, flow cytometry–based evaluation of apoptosis and cell cycle distribution, fluorescence-based morphological analyses, and gene–metabolite interaction analysis. Results: Among the tested compounds, SN-1 exhibited the strongest antiproliferative activity, with IC₂⁽ values of 4.86 ± 0.27 μM in MCF-7 cells and 8.62 ± 1.51 μM in MCF-7/Adr cells, along with a high selectivity index. SN-1 significantly induced apoptosis and caused cell cycle arrest at the G2/M phase in MCF-7 cells and at the G0/G1 phase in MCF-7/Adr cells. Gene enrichment and metabolite interaction analyses revealed modulation of apoptosis-, cell cycle-, and metabolism-related pathways, including associations with glycerol, ATP, and ADP. Discussion: These findings suggest that SN-1 exerts selective anticancer activity against both drug-sensitive and chemoresistant breast cancer cells through the regulation of apoptosis, cell cycle progression, and metabolic pathways. The observed effects on resistant cells further indicate the therapeutic potential of SN-1 in overcoming chemotherapy resistance. Conclusion: The nitro-benzimidazole derivative SN-1 exhibits strong and selective anticancer effects in both drug-sensitive and chemoresistant breast cancer cells by modulating apoptosis, cell cycle progression, and key metabolic pathways.

Paclitaxel (PTX), a taxane-derived chemotherapeutic agent, is frequently used in the treatment of breast cancer (BC). Its anticancer effects are primarily associated with microtubule stabilization, disruption of cell-cycle progression, and triggering of apoptotic cell death. In the present study, we investigated the effects of PTX on the expression of genes involved in cancer-related pathways, energy metabolism, and drug resistance in four molecularly distinct BC cell lines: MCF-7, BT-474, SK-BR-3, and MDA-MB-231. The half-maximal inhibitory concentrations (IC₅₀) of PTX in BC cell lines and the non-tumorigenic hTERT-HME1 breast epithelial cell line were determined by the MTT assay to assess cell cytotoxicity. BC cells were exposed to nine different concentrations of PTX for 24, 48, and 72 h to evaluate concentration- and time-dependent effects. Following treatment, total RNA was isolated and converted into cDNA, and RT-qPCR analysis was performed to investigate PTX-mediated alterations in the expression of genes associated with cancer-related pathways. The impact of PTX on the cell-cycle phase distribution and apoptotic cell death was evaluated by flow cytometry. Treatment with PTX for 48 h at concentrations of 12.60 nM in MCF-7, 5.09 nM in BT-474, 16.09 nM in SK-BR-3, and 36.66 nM in MDA-MB-231 cells reduced cell viability and increased apoptosis. PTX treatment also altered the expression of genes involved in apoptosis, cell-cycle regulation, angiogenesis, epithelial–mesenchymal transition, hypoxia-related signaling, energy metabolism, telomere maintenance, and therapy resistance. Collectively, these findings demonstrate that PTX elicits heterogeneous molecular and cellular responses across molecularly distinct BC cell lines, particularly in cell viability, apoptosis, metabolic regulation, and treatment response. These in vitro findings suggest potential molecular mechanisms that could explain why some cells are more sensitive to PTX than others, but further experimental and clinical validation is needed to confirm this.