The Protective Potential of Butyrate against Colon Cancer Cell Migration and Invasion Is Critically Dependent on Cell Type

IF 4.5 2区农林科学 Q1 FOOD SCIENCE & TECHNOLOGY Molecular Nutrition & Food Research Pub Date : 2024-09-27 DOI:10.1002/mnfr.202400421

Sema Oncel, Bryan D. Safratowich, Huawei Zeng

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Abstract

Scope

Short-chain fatty acids such as butyrate are produced through the fermentation of dietary fiber by colonic bacteria. Preclinical studies indicate an anticancer potential of butyrate, but clinical evidence shows greater variability. The study hypothesizes the effectiveness of butyrate on reducing colon cancer cell migration and invasion may vary due to the cell-type.

Methods and results

The study determines the efficacy of butyrate (0–4 mM) to inhibit cancer cell migration, invasion, and related signaling proteins in three distinct human colorectal cancer (CRC) cell lines: HCT116, HT-29, and Caco-2. Butyrate exhibits a dose-dependent inhibitory effect on cancer cell migration and invasion. This inhibitory potential on oncogenic focal adhesion kinase (FAK) and sarcoma (Src) proteins is greater in HCT116 cells (1.1 and 0.8-fold) and HT-29 cells (0.9 and 0.4-fold) compared to Caco-2 cells, respectively. Conversely, E-cadherin protein, a classical epithelial cell marker and potential tumor suppressor, is 2.3-fold greater in HCT116 cells than in HT-29 cells and Caco-2 cells. Moreover, survival analysis from a public cancer database demonstrates that CRC patients with high E-cadherin expression have a 13% greater 5-year survival rate than those with low expression.

Conclusion

Collectively, butyrate's anti-cancer efficacy on CRC cells varies depending on cell-type and is linked to the FAK/Src/E-cadherin pathway.

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丁酸盐对结肠癌细胞迁移和侵袭的保护作用关键取决于细胞类型

范围丁酸盐等短链脂肪酸是通过结肠细菌发酵膳食纤维产生的。临床前研究表明丁酸盐具有抗癌潜力，但临床证据却显示出更大的差异。本研究假设丁酸盐对减少结肠癌细胞迁移和侵袭的效果可能因细胞类型而异。方法和结果本研究确定了丁酸盐（0-4 mM）在三种不同的人类结肠直肠癌（CRC）细胞系中抑制癌细胞迁移、侵袭和相关信号蛋白的效果：HCT116、HT-29 和 Caco-2。丁酸盐对癌细胞迁移和侵袭具有剂量依赖性抑制作用。与 Caco-2 细胞相比，丁酸盐对 HCT116 细胞（1.1 倍和 0.8 倍）和 HT-29 细胞（0.9 倍和 0.4 倍）中致癌焦点粘附激酶（FAK）和肉瘤（Src）蛋白的抑制潜力更大。相反，E-cadherin 蛋白（一种经典的上皮细胞标记物和潜在的肿瘤抑制因子）在 HCT116 细胞中的含量是 HT-29 细胞和 Caco-2 细胞的 2.3 倍。此外，公共癌症数据库的生存分析表明，E-cadherin 高表达的 CRC 患者的 5 年生存率比低表达的患者高 13%。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Nutrition & Food Research 工程技术-食品科技

CiteScore

8.70

自引率

1.90%

发文量

250

审稿时长

1.7 months

期刊介绍： Molecular Nutrition & Food Research is a primary research journal devoted to health, safety and all aspects of molecular nutrition such as nutritional biochemistry, nutrigenomics and metabolomics aiming to link the information arising from related disciplines: Bioactivity: Nutritional and medical effects of food constituents including bioavailability and kinetics. Immunology: Understanding the interactions of food and the immune system. Microbiology: Food spoilage, food pathogens, chemical and physical approaches of fermented foods and novel microbial processes. Chemistry: Isolation and analysis of bioactive food ingredients while considering environmental aspects.