Nguyen Thi Nga, Trieu Ha Phuong, Nguyen Thi Cuc, Do Thi Phuong, Le Hoang Ngan Ha, Tran Le Nam Khanh, Chu Hoang Ha, Nguyen Trung Nam, Pham Van Cuong, Nguyen Thi Kieu Oanh, Do Thi Thao
Institute of Biotechnology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet Street, Cau Giay District, Hanoi, Vietnam.
University of Science and Technology of Hanoi, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet Street, Cau Giay District, Hanoi, Vietnam.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jun 6. doi: 10.1007/s00210-025-04343-0.
There is a great deal of interest in cancer stem cells (CSCs) in cancer therapy related to hallmarks of stemness and capacity for tumor relapse. Inhibition of CSCs by natural compounds represents a potential therapeutic approach. Thus, this study aimed to investigate potential effects of glyasperin A (GlyA) against CSCs by regulating possible stemness markers and signaling pathways as well. The NCCIT cell, a cell line derived from extragonadal germ cell tumors, was used as the cancer stem cell model for this study. The growth of teratocarcinoma cells under GlyA treatment in two-dimensional (2D) and three-dimensional (3D) cell culture patterns was revealed by MTT assay. The flow cytometry analysis was accessed to determine the expression of stemness surface markers and cell cycle arrest. In addition, the immunoblotting and human phospho-kinase array were applied to determine the possible target molecules in NCCIT cells under GlyA intervention. The collected results revealed that GlyA strongly inhibited the growth of NCCIT cells. The compound made cell cycle progression from the G0/G1 to the S phase. GlyA induced apoptosis by upregulating Bax and phosphorylated ERK1/2 protein levels. On the other hand, it also downregulated the expression of several transcription factors (Nanog, Oct4, c-Myc), which are closely correlated with stemness. Moreover, the levels of some proteins involved in the Akt/mTOR/IKK signaling pathways, which play critical roles in maintaining the self-renewal and proliferative features of CSCs, were also decreased. These results show that GlyA affects multiple targets that sustain the stemness features and proliferation or cell death of CSCs.
在癌症治疗中，人们对癌症干细胞（CSCs）产生了浓厚兴趣，这与干性特征和肿瘤复发能力有关。天然化合物对癌症干细胞的抑制作用代表了一种潜在的治疗方法。因此，本研究旨在通过调节可能的干性标志物和信号通路来研究甘草酸A（GlyA）对癌症干细胞的潜在影响。本研究使用了源自性腺外生殖细胞肿瘤的NCCIT细胞系作为癌症干细胞模型。通过MTT法检测了甘草酸A处理下的畸胎癌细胞在二维（2D）和三维（3D）细胞培养模式下的生长情况。通过流式细胞术分析来确定干性表面标志物的表达和细胞周期停滞。此外，应用免疫印迹法和人类磷酸激酶阵列来确定甘草酸A干预下NCCIT细胞中可能的靶分子。收集的结果表明，甘草酸A强烈抑制NCCIT细胞的生长。该化合物使细胞周期从G0/G1期进入S期。甘草酸A通过上调Bax和磷酸化ERK1/2蛋白水平诱导细胞凋亡。另一方面，它还下调了几种与干性密切相关的转录因子（Nanog、Oct4、c-Myc）的表达。此外，在维持癌症干细胞自我更新和增殖特征中起关键作用的Akt/mTOR/IKK信号通路中一些蛋白质的水平也降低了。这些结果表明，甘草酸A影响多个维持癌症干细胞干性特征、增殖或细胞死亡的靶点。
