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种子衍生肽鲁纳辛通过调节炎症介质、芳香化酶和雌激素受体来抑制乳腺癌细胞的生长。

Seed-derived peptide lunasin suppressed breast cancer cell growth by regulating inflammatory mediators, aromatase, and estrogen receptors.

作者信息

Hsieh Chia-Chien, Wu Chi-Hao, Peng Shih-Han, Chang Chia-Hsin

机构信息

Department of Biochemical Science & Technology, National Taiwan University, Taipei, Taiwan.

School of Life Science, Undergraduate and Graduate Programs of Nutrition Science, National Taiwan Normal University, Taipei, Taiwan.

出版信息

Food Nutr Res. 2023 Jan 26;67. doi: 10.29219/fnr.v67.8991. eCollection 2023.

Abstract

BACKGROUND

Breast cancer is one of the most prevalent cancers in women. Its pathology comprises tumor cells and nearby stromal cells, accompanied by cytokines and stimulated molecules, resulting in a favorable microenvironment for tumor progression. Lunasin is a seed peptide with multiple bioactivities derived from seeds. However, the chemopreventive effect of lunasin on different characteristics of breast cancer has not been fully explored.

OBJECTIVE

This study aims to explore the chemopreventive mechanisms of lunasin through inflammatory mediators and estrogen-related molecules in breast cancer cells.

DESIGN

Estrogen-dependent MCF-7 and independent MDA-MB-231 breast cancer cells were used. The β-estradiol was used to mimic physiological estrogen. The gene expression, mediator secretion, cell vitality, and apoptosis impacting breast malignancy were explored.

RESULTS

Lunasin did not affect normal MCF-10A cell growth but inhibited breast cancer cell growth, increased interleukin (IL)-6 gene expression and protein production at 24 h, and decreased its secretion at 48 h. In both breast cancer cells, aromatase gene and activity and estrogen receptor (ER)α gene expression were decreased by lunasin treatment, while ERβ gene levels were significantly increased in MDA-MB-231 cells. Moreover, lunasin decreased vascular endothelial growth factor (VEGF) secretion and cell vitality and induced cell apoptosis in both breast cancer cell lines. However, lunasin only decreased leptin receptor (Ob-R) mRNA expression in MCF-7 cells. Additionally, β-estradiol increased MCF-7-cell proliferation but not the proliferation of other cells; in particular, lunasin still inhibited MCF-7-cell growth and cell vitality in the presence of β-estradiol.

CONCLUSION

Seed peptide lunasin inhibited breast cancer cell growth by regulating inflammatory, angiogenic, and estrogen-related molecules, suggesting that lunasin is a promising chemopreventive agent.

摘要

背景

乳腺癌是女性中最常见的癌症之一。其病理包括肿瘤细胞和附近的基质细胞,伴有细胞因子和刺激分子,从而形成有利于肿瘤进展的微环境。芦那辛是一种源自种子的具有多种生物活性的种子肽。然而,芦那辛对乳腺癌不同特征的化学预防作用尚未得到充分研究。

目的

本研究旨在探讨芦那辛通过炎症介质和雌激素相关分子在乳腺癌细胞中的化学预防机制。

设计

使用雌激素依赖性MCF-7和非依赖性MDA-MB-231乳腺癌细胞。使用β-雌二醇模拟生理雌激素。探讨影响乳腺恶性肿瘤的基因表达、介质分泌、细胞活力和细胞凋亡。

结果

芦那辛不影响正常MCF-10A细胞生长,但抑制乳腺癌细胞生长,在24小时时增加白细胞介素(IL)-6基因表达和蛋白质产生,并在48小时时减少其分泌。在两种乳腺癌细胞中,芦那辛处理可降低芳香化酶基因和活性以及雌激素受体(ER)α基因表达,而在MDA-MB-231细胞中ERβ基因水平显著增加。此外,芦那辛在两种乳腺癌细胞系中均降低血管内皮生长因子(VEGF)分泌和细胞活力并诱导细胞凋亡。然而,芦那辛仅降低MCF-7细胞中瘦素受体(Ob-R)mRNA表达。此外,β-雌二醇增加MCF-7细胞增殖,但不增加其他细胞的增殖;特别是,在存在β-雌二醇的情况下,芦那辛仍抑制MCF-7细胞生长和细胞活力。

结论

种子肽芦那辛通过调节炎症、血管生成和雌激素相关分子抑制乳腺癌细胞生长,表明芦那辛是一种有前景的化学预防剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17e2/9899045/49d580f5f5af/FNR-67-8991-g001.jpg

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