机构：[1]Key Laboratory of Nutrition and Food Safety of Yunnan Provincial Education Department, Kunming Medical University, Kunming, China[2]Yunnan Provincial Key Laboratory of Public Health and Biosafety & School of Public Health, Kunming Medical University, Kunming, China[3]Key Laboratory of Public Health & Disease Prevention and Control of Yunnan Provincial Education Department, Kunming Medical University, Kunming, China[4]Department of Gastroenterology, Yunnan First People’s Hospital, Kunming, China内科片消化内科云南省第一人民医院[5]Yunnan Yunce Quality Testing Co., Ltd, Kunming, China[6]Department of prevention and health care, Guiyang Second People’s Hospital, Guiyang, China[7]Department of Nutrition, Weifang Second People’s Hospital, Weifang, China[8]Baoshan College of Traditional Chinese Medicine, Baoshan, China
Chemotherapy failure in colorectal cancer patients is the major cause of recurrence and poor prognosis. As a result, there is an urgent need to develop drugs that have a good chemotherapy effect while also being extremely safe. In this study, we found cafestol inhibited colon cancer growth and HCT116 proliferation in vivo and in vitro, and improved the composition of intestinal flora. Further metabolomic data showed that autophagy and AMPK pathways were involved in the process of cafestol's anti -colon cancer effects. The functional validation studies revealed that cafestol increased autophagy vesicles and LC3B-II levels. The autophagic flux induced by cafestol was prevented by using BafA1. The autophagy inhibitor 3 -MA blocked the cafestol-induced increase in LC3B-II and cell proliferation inhibition. Then we found that cafestol induced the increased expressions of LKB1, AMPK, ULK1, p-LKB1, p-AMPK, and p-ULK1 proteins in vivo and in vitro. Using the siRNA targeted to the Lkb1 gene, the levels of AMPK, ULK1, and LC3B-II were suppressed under cafestol treatment. These results indicated that the effect of cafestol is through regulating LKB1/AMPK/ULK1 pathway -mediated autophagic death. Finally, a correlation matrix of the microbiome and autophagy-related proteins was conducted. We found that cafestol-induced autophagic protein expression was positively correlated with the beneficial intestinal bacteria (Muribaculaceae, Bacteroides, Prevotellacece, and Alloprevotella) and negatively correlated with the hazardous bacteria. Conclusions: This study found that cafestol inhibited colon cancer in vitro and in vivo by the mechanism that may be related to LKB1/AMPK/ULK1 pathway -mediated autophagic cell death and improved intestinal microenvironment. (c) 2024 Elsevier Inc. All rights reserved.
基金：
Project of Ten Thousand Talents Program of Yunnan Province [YNWR-QNBJ-2019-042]; Kunming Medical University Biol-ogy Resources Digital Development and Application Project [202002AA100007]
第一作者机构：[1]Key Laboratory of Nutrition and Food Safety of Yunnan Provincial Education Department, Kunming Medical University, Kunming, China[2]Yunnan Provincial Key Laboratory of Public Health and Biosafety & School of Public Health, Kunming Medical University, Kunming, China[3]Key Laboratory of Public Health & Disease Prevention and Control of Yunnan Provincial Education Department, Kunming Medical University, Kunming, China[*2]School of Public Health, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue, Chenggong District, Kunming, 650500, China
共同第一作者：
通讯作者：
通讯机构：[1]Key Laboratory of Nutrition and Food Safety of Yunnan Provincial Education Department, Kunming Medical University, Kunming, China[2]Yunnan Provincial Key Laboratory of Public Health and Biosafety & School of Public Health, Kunming Medical University, Kunming, China[3]Key Laboratory of Public Health & Disease Prevention and Control of Yunnan Provincial Education Department, Kunming Medical University, Kunming, China[5]Yunnan Yunce Quality Testing Co., Ltd, Kunming, China[8]Baoshan College of Traditional Chinese Medicine, Baoshan, China[*1]Baoshan College of Traditional Chinese Medicine, Vocational Education Park, Longyang District, Baoshan, 678000, China[*2]School of Public Health, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue, Chenggong District, Kunming, 650500, China[*3]Yunnan Yunce Quality Testing Co., Ltd, No. 9, Chunman Avenue, Information Industry Base, Luoyang Street Of- fice, Kunming Pilot Free Trade Zone, Economic Development Zone, Yunnan, China
推荐引用方式(GB/T 7714)：
Feng Yuemei,Yang Jizhuo,Wang Yihan,et al.Cafestol inhibits colon cancer cell proliferation and tumor growth in xenograft mice by activating LKB1/AMPK/ULK1-dependent autophagy[J].JOURNAL OF NUTRITIONAL BIOCHEMISTRY.2024,129:doi:10.1016/j.jnutbio.2024.109623.
APA：
Feng, Yuemei,Yang, Jizhuo,Wang, Yihan,Wang, Xue,Ma, Qian...&Yin, Jianzhong.(2024).Cafestol inhibits colon cancer cell proliferation and tumor growth in xenograft mice by activating LKB1/AMPK/ULK1-dependent autophagy.JOURNAL OF NUTRITIONAL BIOCHEMISTRY,129,
MLA：
Feng, Yuemei,et al."Cafestol inhibits colon cancer cell proliferation and tumor growth in xenograft mice by activating LKB1/AMPK/ULK1-dependent autophagy".JOURNAL OF NUTRITIONAL BIOCHEMISTRY 129.(2024)
