Lobaric acid suppresses the stemness potential of colorectal cancer cells through mTOR/AKT

IF 5 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

BioFactors Pub Date : 2025-01-28 DOI:10.1002/biof.70002

Sultan Pulat, Jaycee Augusto Gumiran Paguiri, Chathurika D. B. Gamage, Mücahit Varlı, Rui Zhou, So-Yeon Park, Jae-Seoun Hur, Hangun Kim

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引用次数: 0

Abstract

Stereocaulon alpinum has been found to have potential pharmaceutical properties due to the presence of secondary metabolites such as usnic acid, atranorin, and lobaric acid (LA) which have anticancer activity. On the other hand, the effect of LA on the stemness potential of colorectal cancer (CRC) cells remains unexplored, and has not yet been thoroughly investigated. In this study, we examined the inhibitory activity of LA from Stereocaulon alpinum against the stemness potential of CRC cells and investigated the possible underlying mechanisms. The results demonstrated that LA did not inhibit the cell viability of CSC221 and DLD1. In addition, LA significantly decreased the spheroid formation of CSC221 and DLD1. Moreover, LA treatment suppressed cancer stem cell (CSC) markers; aldehyde dehydrogenase 1 (ALDH1), B-cell-specific Moloney leukemia virus insertion site 1 (BMI1), musashi1 (MSI1), and leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5), along with the sonic hedgehog (Shh) and mTOR/AKT pathways that contribute significantly to maintaining the stemness of CRC cells. Therefore, LA may be a new therapeutic approach for reducing the stemness of CRC cells.

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大巴酸通过mTOR/AKT抑制结直肠癌细胞的干细胞潜能。

由于其次生代谢产物如usnic酸、atanorin和lobaric酸（LA）等具有抗癌活性，已被发现具有潜在的药用价值。另一方面，LA对结直肠癌（CRC）细胞的干性潜能的影响仍未被探索，尚未被彻底研究。在这项研究中，我们检测了立体黄芩提取物LA对结直肠癌细胞干性潜能的抑制活性，并探讨了可能的潜在机制。结果表明，LA未抑制CSC221和DLD1的细胞活力。此外，LA显著降低了CSC221和DLD1的球体形成。此外，LA治疗抑制癌症干细胞（CSC）标志物；醛脱氢酶1 （ALDH1）、b细胞特异性Moloney白血病病毒插入位点1 （BMI1）、musashi1 （MSI1）和富含亮氨酸的重复- g蛋白偶联受体5 (Lgr5)，以及sonic hedgehog （Shh）和mTOR/AKT通路，对维持CRC细胞的干性有重要作用。因此，LA可能是降低CRC细胞干性的一种新的治疗方法。

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

BioFactors 生物-内分泌学与代谢

CiteScore

11.50

自引率

3.30%

发文量

审稿时长

6-12 weeks

期刊介绍： BioFactors, a journal of the International Union of Biochemistry and Molecular Biology, is devoted to the rapid publication of highly significant original research articles and reviews in experimental biology in health and disease. The word “biofactors” refers to the many compounds that regulate biological functions. Biological factors comprise many molecules produced or modified by living organisms, and present in many essential systems like the blood, the nervous or immunological systems. A non-exhaustive list of biological factors includes neurotransmitters, cytokines, chemokines, hormones, coagulation factors, transcription factors, signaling molecules, receptor ligands and many more. In the group of biofactors we can accommodate several classical molecules not synthetized in the body such as vitamins, micronutrients or essential trace elements. In keeping with this unified view of biochemistry, BioFactors publishes research dealing with the identification of new substances and the elucidation of their functions at the biophysical, biochemical, cellular and human level as well as studies revealing novel functions of already known biofactors. The journal encourages the submission of studies that use biochemistry, biophysics, cell and molecular biology and/or cell signaling approaches.