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Limonin Exerts an Anti-Inflammatory Effect through the ERK/MEK Signaling Pathway in Colorectal Cancer
Vol 36, Issue 4, 2022
Abstract
Background: Limonin exhibits multiple biological functions, including anti-cancer, andanti-viral effects. This study aimed to explore the inhibitory effect and potential mechanism of limonin on colorectal cancer (CRC) cells. Methods: In vivo experiments were performed on 30 male F344 rats: 24 rats were used to establish CRC models, and 6 rats were used as blank controls. MTT assay, Hoechst 33342 staining, flow cytometry, and Polymerase Chain Reaction (PCR) assay were performed in vitro to detect the viability of LoVo and SW480 cells affected by limonin. The change in the expression of the factors involved in the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway in CRC cells was assessed in vitro and in vivo by Western blot assay. Hematoxylin and eosin (H&E) staining and immunohistochemistry were used to assessed the changes in the morphology and protein expression of the cancer tissue, respectively. Survival curves were performed. Results: Limonin group showed inhibition of the expression of Cyclin D1 and CDK4 mRNA, enhancement of the expression of p21 and p27 mRNA, blocked cell growth and proliferation leading to G0/G1 phase cell cycle arrestment and apoptosis and downregulation of the expression of ERK/MEK proteins in two CRC cell lines compared to the control group (p < 0.05). The establishment of the CRC model tool went through a total of 8 weeks and the in vivo results revealed that limonin treatment inhibited CRC progression and Ki67 expression, as well as downregulated the expression of ERK/MEK proteins. In addition, after 8 weeks, rats in the control group were heavier than those in the intervention groups, because of the treatment with azoxymethane (AOM) and dextran sulfate sodium (DSS). The survival curve showed that the limonin-treated CRC rats had a longer survival time (p < 0.05). Conclusions: Limonin inhibits CRC by downregulating the expression of the factors involved in the ERK/MEK signaling pathway.
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Copyright (c) 2022 Yue Li, Lin Zhang, Yan Li, Baoyan Shi, Yujuan Zhang
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Medical Genetics, University of Torino Medical School, Italy
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Italy