关键词: Dietary doses Metastasis Sulforaphane Triple-negative breast cancer

Mesh : Isothiocyanates / pharmacology administration & dosage Triple Negative Breast Neoplasms / drug therapy pathology Sulfoxides / pharmacology Female Humans Cell Movement / drug effects Cell Line, Tumor Animals Cell Proliferation / drug effects Mice Anticarcinogenic Agents / pharmacology administration & dosage therapeutic use Lung Neoplasms / drug therapy pathology secondary Xenograft Model Antitumor Assays

来  源:   DOI:10.1038/s41598-024-65455-w   PDF(Pubmed)

Abstract:
Triple-negative breast cancer (TNBC) represents aggressive phenotype with limited treatment options due to the lack of drug targets. Natural compounds are extensively studied regarding their potential to alter the efficacy of cancer treatment Among them sulforaphane - an isothiocyanate of natural origin, was shown to be a hormetic compound, that may exert divergent effects: cytoprotective or cytotoxic depending on its concentrations. Thus, the aim of this study was to determine the effect of its low, dietary concentrations on the proliferation and migration of the TNBC cells in the in vivo and in vitro 2D and 3D model. Results of the in vivo experiment showed up to 31% tumor growth inhibition after sulforaphane treatment associated with lowered proliferating potential of cancer cells, reduced areas of necrosis, and changed immune cell type infiltration, showing less malignant type of tumor in contrast to the non-treated group. Also, the study revealed that sulforaphane decreased the number of lung metastases. The in vitro study confirmed that SFN inhibited cell migration, but only in cells derived from 3D spheroids, not from 2D in vitro cultures. The results show a specific role of sulforaphane in the case of cells released from the TNBC primary tumor and its environment.
摘要:
三阴性乳腺癌(TNBC)表现出侵袭性表型,由于缺乏药物靶标,治疗选择有限。关于天然化合物改变癌症治疗功效的潜力进行了广泛研究,其中萝卜硫烷-天然来源的异硫氰酸酯,被证明是一种恒星化合物,这可能会发挥不同的作用:细胞保护或细胞毒性,这取决于其浓度。因此,这项研究的目的是确定其低,饮食浓度对体内和体外2D和3D模型中TNBC细胞增殖和迁移的影响。体内实验结果显示,萝卜硫烷治疗后肿瘤生长抑制高达31%,与癌细胞增殖潜能降低有关。坏死面积减少,改变了免疫细胞类型的浸润,与未治疗组相比,肿瘤的恶性程度较低。此外,研究显示萝卜硫素减少了肺转移瘤的数量。体外研究证实,SFN抑制细胞迁移,但仅在来自3D球体的细胞中,不是来自2D体外培养。结果表明萝卜硫烷在从TNBC原发肿瘤及其环境中释放的细胞的情况下具有特定的作用。
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