Neogambogic Acid Suppresses Characteristics of Colorectal Cancer Stem Cells Through Inhibition of Wnt/β-catenin Signaling Pathway
10.3971/j.issn.1000-8578.2025.24.1125
- VernacularTitle:新藤黄酸调控Wnt/β-catenin信号通路抑制结肠癌干细胞特性
- Author:
Hao WANG
1
;
Huixian HUANG
1
;
Youran LI
1
;
Yuehua YAN
1
;
Jiaqin YI
1
;
Xiaoyu LIU
1
;
Dongmei LUO
1
;
Yu GU
2
Author Information
1. Anorectal Department, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China.
2. Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China.
- Publication Type:BASICRESEARCH
- Keywords:
Neogambogic acid;
Colorectal cancer;
Colorectal cancer stem cells;
Proliferation;
Apoptosis;
Wnt/β-catenin
- From:
Cancer Research on Prevention and Treatment
2025;52(7):554-561
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the role of neogambogic acid in the characteristics of colorectal cancer stem cells (CRC-CSCs) through the Wnt/β-catenin signaling pathway. Methods The colorectal cells SW480 and HCT166 were divided into control group and neogambogic acid groups (1.5, 3, 6, and 12 μmol/L). The viability of CRC-CSCs was determined by MTT method, and spheroid and clone formation assays were used to assess the capacity of spheroid formation and self-renewal ability of the cells. The effects of neogambogic acid on the apoptosis and cell cycle of CRC-CSCs were evaluated by flow cytometry assays. Real-time quantitative PCR was used to detect the mRNA expression levels of relative markers (CD133, CD44, ALDH1, Oct4, and Nanog) of CRC-CSCs, and the protein expression levels of the self-renewal marker (PCNA), apoptosis markers (cleaved caspase-3 and cleaved caspase-9), and Wnt/β-catenin signaling pathway markers (p-GSK3β, GSK3β, β-catenin, and Wnt) were analyzed using Western blot. Results Compared with the control group, after neogambogic acid treatment, the viability of SW480 and HCT116 cells decreased (P<0.05), the spheroid forming ability and the clone numbers of CRC-CSCs decreased (P<0.001, P<0.01) but the cell apoptosis rate increased (P<0.01), and cell cycle was arrested in G0/G1 phase. Moreover, neogambogic acid downregulated the mRNA and protein expression of relative markers of CRC-CSCs (CD133, CD44, ALDH1, Oct4, and Nanog), PCNA, p-GSK3β, β-catenin, and Wnt (P<0.05) and upregulated the expression of cleaved caspase-3, cleaved caspase-9, and GSK3β (P<0.01). Conclusion Neogambogic can inhibit the stem cell properties of colorectal cells via inhibition of Wnt/β-catenin signaling pathway. As a result, neogambogic acid may be an attractive agent against colorectal cancer.
