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

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.

Leptin–VEGF crosstalk in excess body mass and related disorders: A systematic review

“…Leptin promotes cell proliferation and metastasis of 4T1 breast cancer cells; however, lunasin—a natural seed peptide first identified in soybeans—is able to inhibit metastasis by inhibiting the production of VEGF 53 . Moreover, lunasin inhibits breast cancer cell growth also by decreasing VEGF expression and leptin receptor mRNA expression 54 . The increased risk of breast cancer progression can be associated with the increased expression of proangiogenic factors, such as VEGF A, in THP‐1 macrophages stimulated by leptin synthesized in breast adipocytes 55 .…”

“…53 Moreover, lunasin inhibits breast cancer cell growth also by decreasing VEGF expression and leptin receptor mRNA expression. 54 The increased risk of breast cancer progression can be associated with the increased expression of proangiogenic factors, such as VEGF A, in THP-1 macrophages stimulated by leptin synthesized in breast adipocytes. 55 Also, in a study on human leiomyoma cells, it was found that leptin treatment and adipocyte coculture increases the expression of angiogenic factors, VEGF in this range.…”

The Development of an Isotope Dilution Mass Spectrometry Method for Interleukin-6 Quantification

“…IL-6 plays a crucial role in the tumor microenvironment [10], and it is the most abundant cytokine in this setting. Research results indicate that IL-6 is highly expressed 2 of 13 in almost all types of tumors. For instance, in a study involving 55 patients diagnosed with severe lung cancer, elevated IL-6 levels were found to be significantly associated with poorer performance status and disease progression.…”

“…Patients with high IL-6 levels exhibited worse Eastern Cooperative Oncology Group scores and were more likely to experience disease progression [ 11 ]. The results of recent clinical studies have additionally shown that IL-6 levels are associated with clinical stage, poor prognosis, and survival in patients with various types of cancer, including cervical cancer [ 12 ], breast cancer [ 13 ], ovarian cancer [ 14 ], prostate cancer [ 15 ], and colorectal cancer [ 16 ].…”

Box-Behnken Design Assisted Ultra-Performance Liquid Chromatography-Photodiode Array Detection Method Development, Validation and Quantification of Lunasin Peptide from Nutraceutical Formulation

“…The nontoxic chemopreventive potential of lunasin can be attributed to the 43 amino acid sequence's uniqueness, specifically the presence of a polyaspartyl end at the C-terminus [1] , a highly negatively charged domain with eight aspartic acid residues that appears to bind to deacetylated histones and inhibits mitosis [3,4] . Several studies have reported evidence of lunasin's in vitro and in vivo chemopreventive activity [5][6][7][8][9][10][11][12][13][14][15][16][17] . In the early 2000s, lunasin was purified, identified and quantified from different matrices using ionexchange column chromatography [18][19][20] , sodium dodecyl-sulfate polyacrylamide gel electrophoresis and western blot [18][19][20][21][22] .…”