Protopanaxatriol, a ginsenoside metabolite, induces apoptosis in colorectal cancer cells and arrests their cell cycle by targeting AKT.

IF 5.6 2区 医学 Q1 CHEMISTRY, MEDICINAL
Journal of Ginseng Research Pub Date : 2025-09-01 Epub Date: 2025-04-03 DOI:10.1016/j.jgr.2025.03.012
Yuhao Wang, Jianmei Zhang, Canglang Mou, Yeye Hu, Ziliang He, Jongsung Lee, Jong-Hoon Kim, Jae Youl Cho
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引用次数: 0

Abstract

Background: Colorectal cancer is the third most common cancer worldwide and the fourth leading cause of cancer death. Protopanaxatriol (PPT), one of the main active metabolic ginsenosides of ginseng, has been found to have neuroprotective and anti-inflammatory effects, but its role in regulating colon cancer development remained unclear.

Purpose: We sought to confirm the inhibitory effect of PPT on colon cancer cells and elucidate its target and mechanism.

Methods: MTT assay, colony formation, invasion, migration assays, cell apoptosis, and cell-cycle analysis were performed. Quantitative real-time PCR, Western blotting, bioinformatic analysis using the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology, and cellular thermal shift assay experiments were also employed.

Results: PPT can inhibit the cloning, migration, invasion, and proliferation of colon cancer cells. PPT can increase the number of apoptotic bodies, promote the expression of the apoptotic proteins caspase-9 and caspase-3, induce apoptosis, and inhibit cell proliferation. In addition, by regulating cyclin, PPT can increase the expression of p21 and p27 proteins and inhibit the expression of the cyclin D1 protein, thereby inhibiting the G1/S transformation in the cell cycle. We further demonstrated that PPT can target AKT, reduce its protein expression, and reduce tumor progression and the expression of inflammatory factors caused by AKT high expression (TNF-α, IL-1β, and IL-6), thereby playing a role in inhibiting colon cancer progression.

Conclusion: We are the first to demonstrate that the ginsenoside PPT can inhibit the activity of colon cancer cells by directly binding AKT.

人参皂苷代谢物Protopanaxatriol通过靶向AKT诱导结直肠癌细胞凋亡并阻滞其细胞周期。
背景:结直肠癌是全球第三大常见癌症,也是癌症死亡的第四大原因。原anaxatriol (PPT)是人参中主要的活性代谢人参皂苷之一,已被发现具有神经保护和抗炎作用,但其在调节结肠癌发生中的作用尚不清楚。目的:证实PPT对结肠癌细胞的抑制作用,阐明其作用靶点和机制。方法:MTT法、菌落形成、侵袭、迁移、细胞凋亡、细胞周期分析。采用实时荧光定量PCR、Western blotting、京都基因与基因组百科全书和基因本体生物信息学分析以及细胞热移实验。结果:PPT能抑制结肠癌细胞的克隆、迁移、侵袭和增殖。PPT能增加凋亡小体的数量,促进凋亡蛋白caspase-9和caspase-3的表达,诱导细胞凋亡,抑制细胞增殖。此外,通过调节cyclin, PPT可以增加p21和p27蛋白的表达,抑制cyclin D1蛋白的表达,从而抑制细胞周期中的G1/S转化。我们进一步证明PPT可以靶向AKT,降低其蛋白表达,降低肿瘤进展和AKT高表达引起的炎症因子(TNF-α、IL-1β、IL-6)的表达,从而起到抑制结肠癌进展的作用。结论:我们首次证实人参皂苷PPT通过直接结合AKT抑制结肠癌细胞活性。
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来源期刊
Journal of Ginseng Research
Journal of Ginseng Research CHEMISTRY, MEDICINAL-INTEGRATIVE & COMPLEMENTARY MEDICINE
CiteScore
11.40
自引率
9.50%
发文量
111
审稿时长
6-12 weeks
期刊介绍: Journal of Ginseng Research (JGR) is an official, open access journal of the Korean Society of Ginseng and is the only international journal publishing scholarly reports on ginseng research in the world. The journal is a bimonthly peer-reviewed publication featuring high-quality studies related to basic, pre-clinical, and clinical researches on ginseng to reflect recent progresses in ginseng research. JGR publishes papers, either experimental or theoretical, that advance our understanding of ginseng science, including plant sciences, biology, chemistry, pharmacology, toxicology, pharmacokinetics, veterinary medicine, biochemistry, manufacture, and clinical study of ginseng since 1976. It also includes the new paradigm of integrative research, covering alternative medicinal approaches. Article types considered for publication include review articles, original research articles, and brief reports. JGR helps researchers to understand mechanisms for traditional efficacy of ginseng and to put their clinical evidence together. It provides balanced information on basic science and clinical applications to researchers, manufacturers, practitioners, teachers, scholars, and medical doctors.
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