Pt3R5G inhibits colon cancer cell proliferation through inducing ferroptosis by down-regulating SLC7A11

文献类型： 外文期刊

第一作者： Han, Lin

作者： Han, Lin;Wang, Xiaofei;Fan, Meiyang;Gao, Shanfeng;Zhang, Lingyu;Li, Rufeng;Xiao, Xuan;Ni, Lei;Tong, Dongdong;Huang, Chen;Yang, Juan;Yan, Yamei;Cao, Youlong;Xiong, Xiaofan

作者机构：

关键词： Ferroptosis; RNA sequencing; Anthocyanin; Colon cancer

期刊名称：LIFE SCIENCES （ 影响因子：6.78； 五年影响因子：6.044 ）

ISSN： 0024-3205

年卷期： 2022 年 306 卷

页码：

收录情况： SCI

摘要： Aims: Colon cancer (CC) is a prevalent malignancy worldwide and is one of the most easily altered cancers by dietary regulation. Petunidin 3-O-[rhamnopyranosyl-(trans-p-coumaroyl)]-5-O-(beta-D-glucopyranoside) (Pt3R5G) isolated and purified from Lycium ruthenicum Murray, which exhibits highly efficient antioxidant activity and specific anticancer effects, is the flavonoids compound. We aimed to study the effect of Pt3R5G on CC cells and elucidate the potential underlying mechanisms.Main methods: Cell proliferation was measured by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and colony formation assays. Cell cycle, cell apoptosis and reactive oxygen species (ROS) analysis were performed by flow cytometry. RNA-sequencing was performed to elucidate the potential underlying mechanisms. The lipid peroxidation level of cells was detected by malondialdehyde (MDA) assay. The mito-chondrial morphology of cells was inspected using a transmission electron microscope. Additionally, we over -expressed SLC7A11 to perform rescue experiments. In vivo, xenograft mice assay was performed to verify the effect of Pt3R5G on the growth of colon cancer.Key findings: Pt3R5G reduced the cell activity by blocking the cell cycle in G0/G1 phase, inducing the apoptosis and ferroptosis in RKO cells. The overexpressed of SLC7A11, a significantly down-regulated expression gene caused by Pt3R5G, rescued the cell proliferation inhibition and ferroptosis process. Furthermore, Pt3R5G inhibited tumor growth in nude mice. Our study suggests that Pt3R5G inhibits RKO cell proliferation through mainly reducing ferroptosis by down-regulated SLC7A11.Significance: As a potential therapeutic drug, Pt3R5G showed efficient anticancer activity through a variety of pathways.

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