Skimmianine Modulates Tumor Proliferation and Immune Dynamics in Breast Cancer by Targeting PCNA and TNF-α DOI Creative Commons
Tuğcan Korak, Hayat Ayaz, Fırat Aşır

et al.

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(5), P. 756 - 756

Published: May 20, 2025

Background/Objectives: Breast cancer continues to be a major global health challenge, driving the urgent need for innovative therapeutic strategies. This study evaluates anticancer and immunomodulatory potential of skimmianine in breast through comprehensive approach, integrating biochemical, histopathological, immunohistochemical, bioinformatics analyses. Methods: Thirty-six female Wistar albino rats were divided into three groups: control, 7,12-dimethylbenz[a]anthracene (DMBA)-induced cancer, DMBA + (n = 12/group). was induced with single oral dose 50 mg/kg sesame oil. After 16 weeks, (40 mg/kg) administered intraperitoneally four weeks. Serum CA15-3 levels measured via enzyme-linked immunosorbent assay (ELISA). Histopathological assessment performed using hematoxylin eosin (H&E) staining, proliferating cell nuclear antigen (PCNA) tumor necrosis factor-alpha (TNF-α) evaluated immunohistochemically. Pathway hub gene analyses Cytoscape, functional annotation Enrichr, immune Tumor Immune System Interaction Database (TISIDB) Sangerbox. Results: The burden animals increased after induction compared control groups (0.00 ± 0.00% vs. 89.00 6.60%, respectively, p < 0.001), while treatment significantly reduced (49.00 9.40%, group, 0.191). analysis showed DMBA-induced structural disorganization malignant clustering, whereas preserved ductal structures mitigated damage. Compared administration markedly elevated serum (0.23 0.06 ng/mL 8.57 1.01 ng/mL, respectively), along PCNA (13.0 3.0% 25.0 4.0%, respectively) TNF-α (8.4 1.7% 34.0 5.3%, expression, indicating active progression. Skimmianine (3.72 0.58 ng/mL), (20.0 4.1%), (25.0 3.9%) (p 0.001). In silico indicated skimmianine’s effects on influence cycle pathways, suppression impacts toll-like receptor (TLR) signaling (adjusted 0.05). PCNA- TNF-α-related especially notable basal molecular C2 subtypes Related proteins may regulate dynamics by reducing immunosuppression tumor-promoting inflammation Conclusions: shows promise as therapy simultaneously targeting growth regulation, identified key players.

Language: Английский

Skimmianine Modulates Tumor Proliferation and Immune Dynamics in Breast Cancer by Targeting PCNA and TNF-α DOI Creative Commons
Tuğcan Korak, Hayat Ayaz, Fırat Aşır

et al.

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(5), P. 756 - 756

Published: May 20, 2025

Background/Objectives: Breast cancer continues to be a major global health challenge, driving the urgent need for innovative therapeutic strategies. This study evaluates anticancer and immunomodulatory potential of skimmianine in breast through comprehensive approach, integrating biochemical, histopathological, immunohistochemical, bioinformatics analyses. Methods: Thirty-six female Wistar albino rats were divided into three groups: control, 7,12-dimethylbenz[a]anthracene (DMBA)-induced cancer, DMBA + (n = 12/group). was induced with single oral dose 50 mg/kg sesame oil. After 16 weeks, (40 mg/kg) administered intraperitoneally four weeks. Serum CA15-3 levels measured via enzyme-linked immunosorbent assay (ELISA). Histopathological assessment performed using hematoxylin eosin (H&E) staining, proliferating cell nuclear antigen (PCNA) tumor necrosis factor-alpha (TNF-α) evaluated immunohistochemically. Pathway hub gene analyses Cytoscape, functional annotation Enrichr, immune Tumor Immune System Interaction Database (TISIDB) Sangerbox. Results: The burden animals increased after induction compared control groups (0.00 ± 0.00% vs. 89.00 6.60%, respectively, p < 0.001), while treatment significantly reduced (49.00 9.40%, group, 0.191). analysis showed DMBA-induced structural disorganization malignant clustering, whereas preserved ductal structures mitigated damage. Compared administration markedly elevated serum (0.23 0.06 ng/mL 8.57 1.01 ng/mL, respectively), along PCNA (13.0 3.0% 25.0 4.0%, respectively) TNF-α (8.4 1.7% 34.0 5.3%, expression, indicating active progression. Skimmianine (3.72 0.58 ng/mL), (20.0 4.1%), (25.0 3.9%) (p 0.001). In silico indicated skimmianine’s effects on influence cycle pathways, suppression impacts toll-like receptor (TLR) signaling (adjusted 0.05). PCNA- TNF-α-related especially notable basal molecular C2 subtypes Related proteins may regulate dynamics by reducing immunosuppression tumor-promoting inflammation Conclusions: shows promise as therapy simultaneously targeting growth regulation, identified key players.

Language: Английский

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