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乌洛托品 C 通过 AKT/mTOR 通路抑制结直肠癌进展。

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

机构信息

School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.

Department of Oncology and Cancer Institute, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, China.

出版信息

J Nat Med. 2024 Sep;78(4):887-900. doi: 10.1007/s11418-024-01821-2. Epub 2024 Jun 7.

DOI:10.1007/s11418-024-01821-2
PMID:38849679
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11364574/
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.

摘要

尿石素家族是鞣花酸（EA）的肠道微生物代谢物。虽然尿石素 A（UA）和尿石素 B（UB）已被报道在癌细胞中有抗增殖活性，但尿石素 C（UC）在结直肠癌（CRC）中的作用和相关机制尚未阐明。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 抑制 CRC 细胞的增殖和迁移，诱导细胞凋亡，并将细胞周期阻滞在 G2/M 期，UC 抑制体内皮下移植瘤模型中的肿瘤生长。机制上，UC 通过降低 Y 盒结合蛋白 1（YBX1）的表达来阻断 AKT/mTOR 信号通路的激活。AKT 激动剂 SC79 可逆转 UC 处理的 CRC 细胞中细胞增殖的抑制。总之，我们的研究表明 UC 通过阻断 AKT/mTOR 信号通路来预防 CRC 的进展，提示其可能具有潜在的治疗价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a350/11364574/928421dfb3a7/11418_2024_1821_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a350/11364574/f08e13a1d73b/11418_2024_1821_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a350/11364574/41efa28eb686/11418_2024_1821_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a350/11364574/383e02b4f20c/11418_2024_1821_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a350/11364574/bc1b69306079/11418_2024_1821_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a350/11364574/068f28013d87/11418_2024_1821_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a350/11364574/24767d816a2d/11418_2024_1821_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a350/11364574/928421dfb3a7/11418_2024_1821_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a350/11364574/f08e13a1d73b/11418_2024_1821_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a350/11364574/41efa28eb686/11418_2024_1821_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a350/11364574/383e02b4f20c/11418_2024_1821_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a350/11364574/bc1b69306079/11418_2024_1821_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a350/11364574/068f28013d87/11418_2024_1821_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a350/11364574/24767d816a2d/11418_2024_1821_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a350/11364574/928421dfb3a7/11418_2024_1821_Fig7_HTML.jpg

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