Kang Dong Young, Sp Nipin, Jang Kyoung-Jin, Jo Eun Seong, Bae Se Won, Yang Young Mok
Department of Pathology, School of Medicine, Institute of Biomedical Science and Technology, Konkuk University, Chungju 27478, Republic of Korea.
Pharmacological Research Division, National Institute of Food and Drug Safety Evaluation, Osong Health Technology Administration Complex, Cheongju-si 28159, Republic of Korea.
J Oncol. 2022 Feb 16;2022:6737248. doi: 10.1155/2022/6737248. eCollection 2022.
Embryonic cancer cells (CSCs) could cause different types of cancer, a skill that makes them even more dangerous than other cancer cells. Identifying CSCs using natural products is a good option as it inhibits the recurrence of cancer with moderate various effects. Ursolic acid (UA) is a pentacyclic triterpenoid extracted from fruit and herbal remedies and has known anticancer functions against various cancer cells. However, its potential against CSCs remains uncertain. This study was planned to examine the induction of cell apoptosis by the UA. For cell signaling studies, we performed experiments, which are real-time qPCR and immunoblotting. Also, various cellular processes were analyzed using flow cytometry. The results raised a barrier to cell proliferation by the UA in NTERA-2 and NCCIT cells. Morphological studies also confirmed the UA's ability to cause cell death in embryonic CSCs. Examination of cell death importation showed that the UA formed the expression of the iNOS and thus the cell generation and mitochondrial reactive oxygen generation, which created a reaction to cellular DNA damage by raising the protein levels of phospho-histone ATR and ATM. In addition, the UA created the binding of the G0/G1 cell cycle to NTERA-2 and NCCIT cells, improved the expression levels of p21 and p27, and reduced the expression levels of CDK4, cyclin D1, and cyclin E, confirming the UA's ability to initiate cell cycle arrest. Finally, the UA created an internal mechanism of apoptosis in the embryonic CSC using BAX and cytochrome c regulation as well as the regulation of BCL-xL and BCL-2 proteins. Therefore, UA could be the best candidate for targeting CSCs and thus suppressing the emergence of cancer.
胚胎癌细胞（CSCs）可引发不同类型的癌症，这一特性使其比其他癌细胞更具危险性。利用天然产物识别CSCs是一个不错的选择，因为它能以适度的多种作用抑制癌症复发。熊果酸（UA）是一种从水果和草药中提取的五环三萜类化合物，已知对多种癌细胞具有抗癌作用。然而，其对CSCs的潜在作用仍不确定。本研究旨在检测UA对细胞凋亡的诱导作用。为进行细胞信号研究，我们开展了实时定量PCR和免疫印迹实验。此外，还使用流式细胞术分析了各种细胞过程。结果显示，UA在NTERA - 2和NCCIT细胞中对细胞增殖产生了阻碍。形态学研究也证实了UA导致胚胎CSCs细胞死亡的能力。对细胞死亡导入的检测表明，UA促使诱导型一氧化氮合酶（iNOS）表达，进而导致细胞生成和线粒体活性氧生成，通过提高磷酸化组蛋白ATR和ATM的蛋白质水平对细胞DNA损伤产生反应。此外，UA使G0/G1细胞周期与NTERA - 2和NCCIT细胞结合，提高了p21和p27的表达水平，降低了细胞周期蛋白依赖性激酶4（CDK4）、细胞周期蛋白D1和细胞周期蛋白E的表达水平，证实了UA引发细胞周期停滞的能力。最后，UA通过调节BAX和细胞色素c以及BCL - xL和BCL - 2蛋白，在胚胎CSC中建立了凋亡的内在机制。因此，UA可能是靶向CSCs从而抑制癌症发生的最佳候选物质。
