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HEPATIC NF-kB AND CYR61 SUPPRESSION BY HOLOTHURIA SCABRA METHANOL EXTRACT IN A HIGH-FAT DIET AND DMBA-INDUCED BREAST CANCER MOUSE MODEL

*Demes Chornelia Martantiningtyas orcid  -  Universitas Kristen Maranatha, Indonesia
Raden Ghitas Sariwidyantry  -  Universitas Kristen Maranatha, Indonesia
Open Access Copyright 2025 Demes Chornelia Martantiningtyas, Raden Ghitas Sariwidyantry
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

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Abstract

Background: Liver dysfunction is increasingly recognized in the context of breast cancer progression, particularly due to metastasis and systemic inflammation induced by high-fat diet (HFD)1,2 and carcinogens such as 7,12-dimethylbenz[a]anthracene (DMBA). Although some experimental studies have demonstrated the therapeutic potential of sea cucumber extract, its effect on hepatic gene expression in cancer settings remains underexplored.

Objective: This study investigates the modulatory effects of methanol extract of Holothuria scabra on NF-κB and CYR61 gene expression in the liver of a breast cancer mouse model induced by HFD and DMBA.

Methods: A randomized post-test only control group design was employed using C57BL/6J female mice. Animals were divided into five groups including a normal diet group (ND), a positive control group (HFD + DMBA), and three treatment groups receiving sea cucumber methanol extract (SCME) at doses of 0.33, 0.66, and 0.99 g/kg BW. Liver tissues were harvested for analysis of NF-κB and CYR61 mRNA expression via semi-quantitative RT-PCR.

Results: Mice treated with SCME showed dose-dependent reductions in hepatic NF-κB and CYR61 expression. The highest dose (0.99 g/kg BW) significantly downregulated both genes compared to the HFD + DMBA group (p < 0.05).

Conclusion: SCME modulates inflammatory and tumorigenic gene expression in the liver, suggesting potential anti-inflammatory and anticancer activity. Further studies are needed to explore molecular mechanisms and clinical relevance.

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