Urolithin C suppresses colorectal cancer progression via the AKT/mTOR pathway

IF 2.5 4区医学 Q3 CHEMISTRY, MEDICINAL

Journal of Natural Medicines Pub Date : 2024-06-07 DOI:10.1007/s11418-024-01821-2

Haochi Yang, Binghuo Wu, Qi yang, Tian Tan, Dan Shang, Jie Chen, Chenhui Cao, Chuan Xu

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Abstract

Urolithin families are gut-microbial metabolites of ellagic acid (EA). Although urolithin A (UA) and urolithin B (UB) were reported to have antiproliferative activities in cancer cells, the role and related mechanisms of urolithin C (UC) in colorectal cancer (CRC) have not yet been clarified. In this study, we assess the antitumor activities of UC in vitro and in vivo and further explore the underlying mechanisms in CRC cell lines. We found that UC inhibited the proliferation and migration of CRC cells, induced apoptosis, and arrested the cell cycle at the G2/M phase in vitro, and UC inhibited tumor growth in a subcutaneous transplantation tumor model in vivo. Mechanically, UC blocked the activation of the AKT/mTOR signaling pathway by decreasing the expression of Y-box binding protein 1(YBX1). The AKT agonist SC79 could reverse the suppression of cell proliferation in UC-treated CRC cells. In conclusion, our research revealed that UC could prevent the progression of CRC by blocking AKT/mTOR signaling, suggesting that it may have potential therapeutic values.

Graphical Abstract

Abstract Image

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尿胆素 C 通过 AKT/mTOR 通路抑制结直肠癌进展

尿石素家族是鞣花酸（EA）的肠道微生物代谢产物。虽然有报道称尿石素 A（UA）和尿石素 B（UB）具有抗癌细胞增殖的活性，但尿石素 C（UC）在结直肠癌（CRC）中的作用和相关机制尚未明确。在本研究中，我们评估了 UC 在体外和体内的抗肿瘤活性，并进一步探讨了其在 CRC 细胞系中的潜在机制。我们发现，UC 在体外能抑制 CRC 细胞的增殖和迁移，诱导细胞凋亡，并使细胞周期停滞在 G2/M 期；在体内皮下移植肿瘤模型中，UC 能抑制肿瘤生长。UC通过降低Y-box结合蛋白1（YBX1）的表达，从机制上阻断了AKT/mTOR信号通路的激活。AKT激动剂SC79能逆转UC对CRC细胞增殖的抑制。总之，我们的研究发现，UC可以通过阻断AKT/mTOR信号传导阻止CRC的进展，这表明它可能具有潜在的治疗价值。

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来源期刊

Journal of Natural Medicines 医学-药学

CiteScore

6.90

自引率

3.00%

发文量

审稿时长

1.7 months

期刊介绍： The Journal of Natural Medicines is an international journal publishing original research in naturally occurring medicines and their related foods and cosmetics. It covers: -chemistry of natural products -biochemistry of medicinal plants -pharmacology of natural products and herbs, including Kampo formulas and traditional herbs -botanical anatomy -cultivation of medicinal plants. The journal accepts Original Papers, Notes, Rapid Communications and Natural Resource Letters. Reviews and Mini-Reviews are generally invited.