Regulation of Human Colorectal Cancer Cells in Tumor Spheroids by Sodium Butyrate.

IF 1.7 4区医学 Q3 PHARMACOLOGY & PHARMACY

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI:10.1248/bpb.b25-00043

Yuzuki Takahama, An Kadoi, Yuno Tauchi, Satsuki Kasahara, Kyota Ishii, Tomohiro Yano

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Abstract

Butyrate exerts strong anti-colorectal cancer effects via epigenetic regulation. However, whether butyrate has a negative impact on colorectal cancer in vivo remains unclear. Therefore, this study aimed to investigate whether butyric acid can regulate the growth of colorectal cancer cells using spheroids as an in vivo model. A three-dimensional (3D) culture system was used to form spheroids from the human colorectal cancer cell line HT-29. Spheroids formed in the 3D culture system exhibited some malignant cancer phenotypes (increased cancer stem cell marker levels, anticancer drug resistance, and G0/G1 phase accumulation in the cell cycle) compared with cells in the two-dimensional cell culture system. Sodium butyrate (SB) treatment suppressed cancer stem cell marker levels in spheroids and induced differentiation by increasing the alkaline phosphatase activity. Additionally, SB-induced changes in genes related to cell cycle control indicated that SB reactivated the cell cycle in spheroids, regulating the transition from the G0 to G1 phase. Furthermore, SB treatment induced cell death via apoptosis, which might be due to G1 arrest in the cell cycle. In conclusion, SB induced the differentiation and subsequent cell death of HT-29-derived cancer cells in spheroids, highlighting its potential as a novel anticancer agent for colorectal cancer.

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丁酸钠调节人结直肠癌细胞在肿瘤球体中的作用。

丁酸盐通过表观遗传调控发挥强大的抗结直肠癌作用。然而，体内丁酸盐是否对结直肠癌有负面影响尚不清楚。因此，本研究旨在探讨丁酸是否可以调节大肠癌细胞的生长，以球体为体内模型。采用三维（3D）培养系统从人结直肠癌细胞系HT-29中培养球形细胞。与二维细胞培养系统中的细胞相比，在三维培养系统中形成的球形细胞表现出一些恶性肿瘤表型（癌症干细胞标志物水平升高、抗癌药物耐药、细胞周期中G0/G1期积累）。丁酸钠（SB）通过增加碱性磷酸酶活性抑制肿瘤干细胞球形标记物水平并诱导分化。此外，SB诱导的细胞周期控制相关基因的变化表明SB在球状体中重新激活细胞周期，调节从G0期到G1期的转变。此外，SB处理通过凋亡诱导细胞死亡，这可能是由于细胞周期中的G1阻滞。综上所述，SB可诱导ht -29衍生的癌细胞在球状体中分化和随后的细胞死亡，这凸显了其作为一种新型结直肠癌抗癌药物的潜力。

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

Biological & pharmaceutical bulletin 医学-药学

CiteScore

3.50

自引率

5.00%

发文量

247

审稿时长

2 months

期刊介绍： Biological and Pharmaceutical Bulletin (Biol. Pharm. Bull.) began publication in 1978 as the Journal of Pharmacobio-Dynamics. It covers various biological topics in the pharmaceutical and health sciences. A fourth Society journal, the Journal of Health Science, was merged with Biol. Pharm. Bull. in 2012. The main aim of the Society’s journals is to advance the pharmaceutical sciences with research reports, information exchange, and high-quality discussion. The average review time for articles submitted to the journals is around one month for first decision. The complete texts of all of the Society’s journals can be freely accessed through J-STAGE. The Society’s editorial committee hopes that the content of its journals will be useful to your research, and also invites you to submit your own work to the journals.