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      Ursolic acid inhibits the metastasis of colon cancer by downregulating ARL4C expression

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          Abstract

          Ursolic acid (UA), a natural pentacyclic triterpenoid, is known to exhibit various biological activities and anticancer effects. However, the underlying anticancer mechanism is not fully understood to date. The present study aimed to investigate the antimetastatic effect of UA through ADP-ribosylation factor like GTPase 4C (ARL4C) in colon cancer. A lung metastasis model of colon cancer in nude mice was established through tail vein injection. A Cell Counting Kit-8 assay was used to investigate the proliferation of colon cancer cells. Transwell assays were used to detect cell migration and invasion. The expression levels of proteins including ARL4C, matrix metallopeptidase 2 (MMP2), phosphorylated (p)-AKT and p-mTOR were measured using western blot analysis. Immunohistochemistry was used to determine the protein expression level in tissues. ARL4C ubiquitination levels were analysed using immunoprecipitation and western blotting. The results indicated that UA inhibits the metastasis of colon cancer in vivo and in vitro. The expression of ARL4C in human colon cancer tissue was significantly higher than that in adjacent tissues and its high expression level was associated with lymph node metastases and tumour stage. UA treatment significantly decreased ARL4C and MMP2 protein levels and inhibited the AKT/mTOR signalling pathway. Overexpression of ARL4C reversed the inhibitory effect of UA on the invasion and migration of HCT-116 and SW480 cells, as well as the expression and secretion of MMP2 protein. In addition, UA and an AKT signalling pathway inhibitor (LY294002) induced the ubiquitination of the ARL4C protein, which was reversed by a proteasome inhibitor (MG-132). Collectively, it was revealed in the present study that UA served as a novel solution to relieve colon cancer metastasis by inducing the ubiquitination-mediated degradation of ARL4C by modulating the AKT signalling pathway. Thus, UA may be a promising treatment option to prolong the survival of patients with colon cancer metastasis.

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          Hyuna Sung, Jacques Ferlay, Rebecca Siegel … (2021)
          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            Akt in cancer: mediator and more

            Sundaramoorthy Revathidevi, Arasambattu Kannan Munirajan (2019)
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              Perspectives for cancer prevention with natural compounds.

              A R M Ruhul Amin, Omer Kucuk, Fadlo Khuri … (2009)
              Cancer is the second leading cause of death in the United States. Despite the estimated 565,650 deaths in 2008 of Americans as a result of cancer, it is mostly a preventable disease. Simply by modification of diet, maintenance of optimum body weight, and regular physical activity, 30% to 40% of all instances of cancer could be prevented. Modification of diet alone by increasing vegetable and fruit intake could prevent 20% or more of all cases of cancer and may potentially prevent approximately 200,000 cancer-related deaths annually. Because of their safety, low toxicity, antioxidant properties, and general acceptance as dietary supplements, fruits, vegetables, and other dietary elements (phytochemicals and minerals) are being investigated for the prevention of cancer. Extensive research over the past several decades has identified numerous dietary and botanical natural compounds that have chemopreventive potential. In this review, we discuss promising natural chemopreventive compounds, their molecular targets, and their mechanisms, which may help the further design and conduct of preclinical and clinical trials.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Oncol Rep
                Journal ID (iso-abbrev): Oncol Rep
                Title: Oncology Reports
                Publisher: D.A. Spandidos
                ISSN (Print): 1021-335X
                ISSN (Electronic): 1791-2431
                Publication date Collection: February 2024
                Publication date (Electronic): 18 December 2023
                Publication date PMC-release: 18 December 2023
                Volume: 51
                Issue: 2
                Electronic Location Identifier: 27
                Affiliations
                [1 ]Department of Laboratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China
                [2 ]Department of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China
                Author notes
                Correspondence to: Professor Xiangdong Kang or Professor Rong Wu, Department of Laboratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 164 Lanxi Road, Putuo, Shanghai 200062, P.R. China, E-mail: rong701126.com xd_kang@ 123456163.com
                [*]

                Contributed equally

                Article
                Publisher ID: OR-51-2-08686
                DOI: 10.3892/or.2023.8686
                PMC ID: 10777457
                PubMed ID: 38131251
                SO-VID: 73376357-8626-4926-9717-207fcb226404
                Copyright © Copyright: © Zhang et al.
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                Date received : 29 June 2023
                Date accepted : 08 November 2023
                Funding
                Funded by: Scientific Research Fund of Shanghai Sixth People's Hospital Medical Group
                Award ID: 22-LY-02
                Funded by: One Hundred Talents Project of Putuo Hospital, Shanghai University of Traditional Chinese Medicine
                Award ID: 2022-RCQH-03
                Funded by: Science and Technology Innovation Project of Putuo District Health System
                Award ID: ptkwws202307
                Funded by: National Natural Science Foundation of China
                Award ID: 82305141
                The present study was supported from the Scientific Research Fund of Shanghai Sixth People's Hospital Medical Group (grant no. 22-LY-02), the One Hundred Talents Project of Putuo Hospital, Shanghai University of Traditional Chinese Medicine (grant no. 2022-RCQH-03), the Science and Technology Innovation Project of Putuo District Health System (grant no. ptkwws202307) and the National Natural Science Foundation of China (grant no. 82305141).
                Categories
                Subject: Articles

                Keywords: ursolic acid,adp ribosylation factor like gtpase 4c,akt,colon cancer,metastasis
                Data availability:
                Keywords: ursolic acid, adp ribosylation factor like gtpase 4c, akt, colon cancer, metastasis

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