Sialic Acid-Binding Lectin from Bullfrog Eggs Exhibits an Anti-Tumor Effect Against Breast Cancer Cells Including Triple-Negative Phenotype Cells.

Takeo Tatsuta,Masahiro Hosono,Toshiyuki Sato,Akiyoshi Hara,Tsuneyoshi Suzuki,Shoko Sato,Shigeki Sugawara

doi:10.3390/molecules23102714

Takeo Tatsuta, Masahiro Hosono + Show 5 more

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https://doi.org/10.3390/molecules23102714

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Abstract

Sialic acid-binding lectin from Rana catesbeiana eggs (cSBL) is a multifunctional protein that has lectin and ribonuclease activity. In this study, the anti-tumor activities of cSBL were assessed using a panel of breast cancer cell lines. cSBL suppressed the cell growth of all cancer cell lines tested here at a concentration that is less toxic, or not toxic at all, to normal cells. The growth suppressive effect was attributed to the cancer-selective induction of apoptosis. We assessed the expressions of several key molecules associated with the breast cancer phenotype after cSBL treatment by western blotting. cSBL decreased the expression level of estrogen receptor (ER) α, while it increased the phosphorylation level of p38 mitogen-activated protein kinase (MAPK). cSBL also suppressed the expression of the progesterone receptor (PgR) and human epidermal growth factor receptor type 2 (HER2). Furthermore, it was revealed that cSBL decreases the expression of the epidermal growth factor receptor (EGFR/HER1) in triple-negative breast cancer cells. These results indicate that cSBL induces apoptosis with decreasing ErbB family proteins and may have great potential for breast cancer chemotherapy, particularly in triple-negative phenotype cells.

Highlights

Lectins are proteins that bind to specific carbohydrate structures
We found that treatment with catesbeiana sialic acid-binding lectin (cSBL) leads to the decrement of human epidermal growth factor receptor type 2 (HER2) expression, and this reduced expression was observed with regard to other ErbB family proteins expressed in each cell line
The effects of cSBL on the breast cancer cell growth and on the expression of molecules that play key roles in breast cancer prognosis were evaluated. cSBL significantly suppressed the cell growth of six cancer cell lines representing a variety of phenotypes in ERα, progesterone receptor (PgR), and HER2 (Table 1 and Figure 1) through the induction of apoptosis (Figure 2)

Summary

Introduction

Lectins are proteins that bind to specific carbohydrate structures. They exist universally in plants, microorganisms, and animals, and have great potential for cancer therapy [1]. The 12 kDa protein isolated from Rana catesbeiana oocytes was found to be a cell agglutinin [8] of many kinds of cancer cells, but not normal cells. These agglutinations were shown to be inhibited by Molecules 2018, 23, 2714; doi:10.3390/molecules23102714 www.mdpi.com/journal/molecules

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