Curcumin suppresses cell proliferation and reduces cholesterol absorption in Caco-2 cells by activating the TRPA1 channel

作者全名："Qin, Si; Su, Qian; Li, Xiang; Shao, Muqing; Zhang, Yindi; Yu, Fadong; Ni, Yinxing; Zhong, Jian"

作者地址："[Qin, Si; Su, Qian; Shao, Muqing; Zhang, Yindi; Yu, Fadong; Ni, Yinxing; Zhong, Jian] Chongqing Med Univ, Dept Endocrinol, Affiliated Hosp 3, 1 Shuanghu Branch Rd, Chongqing 401120, Peoples R China; [Li, Xiang] Peking Univ, Coll Chem & Mol Engn, Beijing 100871, Peoples R China"

通信作者："Ni, YX; Zhong, J (通讯作者)，Chongqing Med Univ, Dept Endocrinol, Affiliated Hosp 3, 1 Shuanghu Branch Rd, Chongqing 401120, Peoples R China."

来源：LIPIDS IN HEALTH AND DISEASE

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000915892600001

JCR分区：Q2

影响因子：3.9

年份：2023

卷号：22

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Cholesterol absorption; Curcumin; Caco-2 cells; NPC1L1; Proliferation; TRPA1

摘要："Background Curcumin (Cur) is a bioactive dietary polyphenol of turmeric with various biological activities against several cancers. Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths. Intestinal cholesterol homeostasis is associated with CRC. Chemotherapy for CRC is related to varied adverse effects. Therefore, natural products with anti-cancer properties represent a potential strategy for primary prevention of CRC.Methods The present study used Cur as a therapeutic approach against CRC using the Caco-2 cell line. The cells were treated with different concentrations of Cur for different duration of time and then the proliferation ability of cells was assessed using Cell Counting Kit-8 and 5-Ethynyl-2 ' -deoxyuridine assays. Oil red O staining and cholesterol assay kit were used to evaluate cellular lipid content and cholesterol outward transportation. Finally, the protein expressions of cholesterol transport-related protein and signal transduction molecules were assessed using Western blot assay.Results Cur inhibited cell proliferation in Caco-2 cells in a dose- and time-dependent manner by activating the transient receptor potential cation channel subfamily A member 1 (TRPA1) channel. Activation of the TRPA1 channel led to increased intracellular calcium, peroxisome proliferator-activated receptor gamma (PPAR gamma) upregulation, and the subsequent downregulation of the specificity protein-1 (SP-1)/sterol regulatory element-binding protein-2 (SREBP-2)/Niemann-Pick C1-like 1 (NPC1L1) signaling pathway-related proteins, and finally reduced cholesterol absorption in Caco-2 cells.Conclusions Cur inhibits cell proliferation and reduces cholesterol absorption in Caco-2 cells through the Ca2+/PPAR gamma/SP-1/SREBP-2/NPC1L1 signaling by activating the TRPA1 channel, suggesting that Cur can be used as a dietary supplement for the primary prevention of CRC."

基金机构：National Natural Science Foundation of China [81670382]; Third Affiliated Hospital of Chongqing Medical University [KY20075]; Chongqing Municipality [B201710]

基金资助正文：This work was supported by the National Natural Science Foundation of China [grant no. 81670382]; the "Research Incubation Project" of the Third Affiliated Hospital of Chongqing Medical University [grant no. KY20075]; and the "Sports Scientific Research Project" of Chongqing Municipality [grant no. B201710].