Cell Biology International最新文献

Colorectal cancer (CRC) remains a significant global health burden, necessitating the exploration of novel therapeutic strategies. Tocotrienols (T3s), particularly gamma (γ)- and delta (δ)-T3 isoforms, exhibit promising anticancer properties. This study investigates the antiproliferative effects of γT3 and δT3 on HCC2998 human colorectal carcinoma cells, elucidating their underlying molecular mechanisms through cell viability assays and comprehensive gene expression profiling. The half-maximal inhibitory concentrations (IC₅₀) for γT3 were determined to be 12.59 ± 0.35 µg/mL (24 h), 11.63 ± 0.05 µg/mL (48 h), and 10.92 ± 0.06 µg/mL (72 h). For δT3, the IC₅₀ values were lower: 9.66 ± 0.17 µg/mL (24 h), 9.33 ± 0.00 µg/mL (48 h), and 9.69 ± 0.05 µg/mL (72 h). Microarray analysis revealed that histone modification pathways were most significantly affected, profoundly influencing the DNA damage response (DDR). Specifically, treatment with γT3 and δT3 led to the upregulation of the ATM tumor suppressor gene and downregulation of key DDR-related genes, including BID, BRCA1, CCNE2, CDC25A, CDC25C, CDK2, E2F1, H2AFX, PMAIP1, RAD51, and SMC1A. These findings indicate that γT3 and δT3 inhibit HCC2998 cell proliferation by activating the DDR pathway, highlighting their potential as therapeutic agents to overcome cell cycle arrest resistance in CRC. This study provides critical insights into the molecular actions of γT3 and δT3, supporting their further investigation as promising candidates for CRC intervention.

Doxorubicin (DOX), although widely used as a potent chemotherapeutic agent, is limited by its dose-dependent cardiotoxicity. Esculetin (E), a naturally occurring coumarin derivative, has been reported to exert antioxidant and anti-apoptotic effects in various tissues. This study aimed to evaluate the cardioprotective effects of esculetin against DOX-induced cardiac injury in rats by examining changes in the expression of genes related to apoptosis, oxidative stress, and mitochondrial function. Male Wistar rats were randomly assigned into six groups (Control, DOX, E50, E100, DOX + E50, DOX + E100). Cardiotoxicity was induced by administering DOX was administered as six intraperitoneal injections of 5 mg/kg each over 14 days (cumulative dose = 30 mg/kg). Serum cardiac markers (CK-MB, LDH, and cTn-I) were measured, and cardiac tissues were subjected to histopathological examination and RT-qPCR analysis for target gene expression. In addition, hierarchical clustering heatmap was employed to evaluate multidimensional gene expression patterns across groups. DOX treatment significantly elevated serum cardiac injury markers and upregulated pro-apoptotic genes (Casp3, Casp9, Anf, Bnp, β-Mhc), while downregulating genes associated with mitochondrial biogenesis (Pgc1α) and antioxidant response (Foxo1, Cox2). These findings suggest esculetin as a potential adjunctive candidate for cardioprotection during DOX chemotherapy. However, given the absence of protein-level validation, further studies are warranted to confirm whether the observed gene expression changes translate into corresponding alterations at the protein level.

Peritumoral adipocytes that exhibit changes in their phenotype and distinct biological characteristics, such as reduced expression of mature adipocyte differentiation markers, increased secretion of adipocyte-derived factors, and facilitation of metabolic reprogramming in cancer cells, are referred to as cancer-associated adipocytes (CAAs). CAAs are increasingly recognized as important contributors to tumor initiation, progression, and metastasis within the tumor microenvironment (TME). Found predominantly in fat-rich tissues such as breast, ovarian, colorectal, and pancreatic cancers, CAAs undergo significant functional changes when exposed to cancer cells. These changes include lipid transfer to cancer cells, secretion of pro-inflammatory cytokines, and remodeling of the extracellular matrix, all of which enhance cancer cell survival, proliferation, and invasion. The TME, composed of various non-cancerous cells, extracellular matrix components, and signaling molecules, plays a dynamic role in influencing tumor behavior and treatment response. CAAs engage in a reciprocal interaction with cancer cells, transforming from normal adipocytes to tumor-promoting cells while simultaneously driving cancer aggressiveness. Understanding the mechanisms through which CAAs contribute to cancer progression offers promising avenues for novel therapeutic strategies targeting the TME to combat cancer more effectively.

This study evaluated the cytotoxic and genotoxic potential of lercanidipine hydrochloride (LHC) on human peripheral lymphocytes using in vitro and in silico approaches. The micronucleus (MN) test revealed a significant, dose-dependent increase in MNs, particularly after 24-h treatment (***p < 0.001), which suggests potential DNA damage. However, the chromosome aberration (CA) test did not yield statistically significant results, although a dose-related upward trend was observed. A substantial reduction in both the mitotic index (MI) and the nuclear division index (NDI) was observed at all concentrations (**p < 0.01, ***p < 0.001), indicating strong cytotoxic effects. In silico molecular docking analysis revealed that the ligand (LHC) binds to the minor groove of B-DNA with a binding energy of −7.7 kcal/mol, forming non-covalent interactions similar to those of the known minor groove binder Netropsin (−8.14 kcal/mol). By contrast, the positive control, mitomycin C (MMC), binds to the major groove via intercalation, forming covalent cross-links, with a binding energy of −5.45 kcal/mol. Although LHC's minor groove binding suggests a potential preference for AT-rich regions, its sequence specificity remains unconfirmed. Overall, these findings suggest that LHC primarily exhibits cytotoxic effects (e.g., inhibition of DNA replication or transcription), with only limited and preliminary evidence of genotoxic potential. Further studies are needed to elucidate the safety of LHC and its DNA interaction mechanisms.

Endotoxin-induced uveitis (EIU) is a well-established model for acute ocular inflammation and mimics aspects of human uveitis. Tauroursodeoxycholic acid (TUDCA), a bile acid with known anti-inflammatory and cytoprotective properties, may attenuate retinal injury by targeting endoplasmic reticulum (ER) stress and apoptosis. This study investigates the protective effects of TUDCA in both in vivo and in vitro EIU models. EIU was induced in male Wistar rats by intravitreal injection of lipopolysaccharide (LPS), with or without prior intraperitoneal TUDCA administration. ARPE-19 cells were used to model retinal pigment epithelial stress in vitro. Ocular inflammation was assessed clinically and histologically. Immunostaining and immunofluorescence quantified ER stress marker Glucose-Regulated Protein 78 (GRP78), caspase-3, caspase-12, and apoptosis. Caspase-3 activity and TUNEL assays evaluated apoptotic response. TUDCA pretreatment significantly reduced LPS-induced ocular inflammation and retinal thickening in rats. In ARPE-19 cells, TUDCA restored LPS-compromised viability and mitigated morphological damage. Both models showed reduced expression of GRP78, caspase-3, and caspase-12 following TUDCA administration. TUNEL and caspase-3 activity assays confirmed that TUDCA decreased apoptosis in retinal tissues and cultured cells. The findings demonstrate that TUDCA effectively suppresses ER stress and apoptosis pathways activated during endotoxin-induced retinal inflammation. Its dual anti-inflammatory and cytoprotective actions support its therapeutic potential in acute ocular inflammatory conditions. TUDCA attenuates clinical, histological, and molecular manifestations of LPS-induced uveitis, highlighting its promise as a candidate for adjunctive therapy in inflammatory retinal diseases.

Cystic fibrosis (CF) is an inherited, autosomal recessive disorder that is caused by mutations in the gene encoding cystic fibrosis transmembrane conductance regulator (CFTR). CFTR maintains the balance between water and salts by transporting chloride ions along various epithelial surfaces. CFTR impairment affects the function of several organs, including the lungs. Newborn screening, prenatal diagnosis, and pharmacological interventions have altered the prevalence and incidence of cystic fibrosis. Although CFTR modulators are a promising treatment option, their ability to target and correct only one mutation at a time restricts their therapeutic potential. The development of genome editing technologies such as Clustered Regularly Interspaced Short Palindromic Repeats-Cas(CRISPR-Cas9) has the potential to correct genetic mutations, including those associated with CF, thereby offering a permanent treatment by fixing the root cause of CF. This article summarizes cystic fibrosis development, prognosis, and diagnosis, as well as possibilities for correcting various types of CFTR gene mutations. The review focuses on the potential of gene editing technologies to repair CFTR mutations and their applications in the advancement of CF treatment.