Plectalibertellenone A suppresses colorectal cancer cell motility and glucose metabolism by targeting TGF‐β/Smad and Wnt pathways

IF 5 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

BioFactors Pub Date : 2024-09-18 DOI:10.1002/biof.2120

Chathurika D. B. Gamage, Jeong‐Hyeon Kim, Rui Zhou, So‐Yeon Park, Sultan Pulat, Mücahit Varlı, Sang‐Jip Nam, Hangun Kim

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引用次数: 0

Abstract

Colorectal cancer (CRC) is the second most common cause of cancer‐related death and represents a serious worldwide health problem. CRC metastasis decreases the survival rate of cancer patients, underscoring the need to identify novel anticancer agents and therapeutic targets. Here, we introduce Plectalibertellenone A (B) as a promising agent for the inhibition of CRC cell motility and glucose metabolism and explore its mechanism of action in CRC cells. Plectalibertellenone A suppressed TGF‐β gene expression and the activation of the TGF‐β/Smad signaling pathway, leading to reverse epithelial to mesenchymal transition (EMT) by modulating the expressions of EMT markers and transcriptional factors such as E‐cadherin, N‐cadherin, vimentin, Slug, Snail, Twist, and ZEB1/2. Furthermore, disruption of Wnt signaling inhibited CRC motility and glucose metabolism including glycolysis and oxidative phosphorylation, primarily affecting glycolytic enzymes, GLUT1, HK2, PKM2, LDHA, and HIF‐1α under hypoxic condition. Therefore, Plectalibertellenone A is a potential drug candidate that can be developed into a promising anticancer treatment to prevent CRC metastasis and inhibit glucose metabolism.

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折衷贝特硒酮 A 通过靶向 TGF-β/Smad 和 Wnt 通路抑制结直肠癌细胞运动和葡萄糖代谢

结肠直肠癌（CRC）是导致癌症相关死亡的第二大常见病因，是一个严重的世界性健康问题。CRC 转移会降低癌症患者的生存率，因此需要找到新型抗癌药物和治疗靶点。在此，我们介绍了一种有望抑制 CRC 细胞运动和葡萄糖代谢的药物 Plectalibertellenone A (B)，并探讨了它在 CRC 细胞中的作用机制。Plectalibertellenone A抑制了TGF-β基因的表达和TGF-β/Smad信号通路的激活，通过调节E-cadherin、N-cadherin、vimentin、Slug、Snail、Twist和ZEB1/2等EMT标志物和转录因子的表达，导致上皮向间充质转化（EMT）的逆转。此外，Wnt 信号的中断抑制了 CRC 的运动和糖代谢，包括糖酵解和氧化磷酸化，主要影响缺氧条件下的糖酵解酶、GLUT1、HK2、PKM2、LDHA 和 HIF-1α。因此，Plectalibertellenone A 是一种潜在的候选药物，可以开发成一种很有前景的抗癌疗法，以防止 CRC 转移并抑制糖代谢。

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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.