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      Ursolic acid enhances the therapeutic effects of oxaliplatin in colorectal cancer by inhibition of drug resistance

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          Abstract

          It has been reported that ursolic acid has anti‐tumor activity and it enhances the therapeutic effect of oxaliplatin in colorectal cancer ( CRC). However, the underlying mechanisms remain unknown. In the present study, the mechanisms of the enhancement of therapeutic effects through use of ursolic acid were investigated. We treated CRC cell lines HCT8 and SW480 with ursolic acid and oxaliplatin and monitored the effects on cell proliferation, apoptosis, reactive oxygen species ( ROS) production and drug resistance gene production. We discovered that treatment with a combination of ursolic acid and oxaliplatin resulted in significant inhibition of cell proliferation, significantly increased apoptosis and ROS production, and significant inhibition of drug resistance gene expression. Our study provided evidence that ursolic acid enhances the therapeutic effects of oxaliplatin in colorectal cancer by ROS‐mediated inhibition of drug resistance.

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          Persistent oxidative stress in cancer.

          S Toyokuni, K. Okamoto, J Yodoi … (1995)
          DNA of cancers such as renal cell carcinoma and mammary invasive ductal carcinoma, is persistently exposed to more oxidative stress than that of adjacent normal tissue. We suggest that the concept of 'persistent oxidative stress in cancer' may open up a new research area, explaining part of the characteristic tumor biology of cancer such as activated transcription factors and proto-oncogenes, genomic instability, chemotherapy-resistance, invasion and metastasis.
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            Role of Reactive Oxygen Species (ROS) in Therapeutics and Drug Resistance in Cancer and Bacteria.

            Allimuthu T. Dharmaraja (2017)
            Evading persistent drug resistance in cancer and bacteria is quintessential to restore health in humans, and impels intervention strategies. A distinct property of the cancer phenotype is enhanced glucose metabolism and oxidative stress. Reactive oxygen species (ROS) are metabolic byproducts of aerobic respiration and are responsible for maintaining redox homeostasis in cells. Redox balance and oxidative stress are orchestrated by antioxidant enzymes, reduced thiols and NADP(H) cofactors, which is critical for cancer cells survival and progression. Similarly, Escherichia coli (E. coli) and life-threatening infectious pathogens such as Staphylococcus aureus (SA) and Mycobacterium tuberculosis (Mtb) are appreciably sensitive to changes in the intracellular oxidative environment. Thus, small molecules that modulate antioxidant levels and/or enhance intracellular ROS could disturb the cellular oxidative environment and induce cell death, and hence could serve as novel therapeutics. Presented here are a collection of approaches that involve ROS modulation in cells as a strategy to target cancer and bacteria.
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              Ursolic Acid—A Pentacyclic Triterpenoid with a Wide Spectrum of Pharmacological Activities

              Łukasz Woźniak, Sylwia Skąpska, Krystian Marszałek (2015)
              Ursolic acid (UA) is a natural terpene compound exhibiting many pharmaceutical properties. In this review the current state of knowledge about the health-promoting properties of this widespread, biologically active compound, as well as information about its occurrence and biosynthesis are presented. Particular attention has been paid to the application of ursolic acid as an anti-cancer agent; it is worth noticing that clinical tests suggesting the possibility of practical use of UA have already been conducted. Amongst other pharmacological properties of UA one can mention protective effect on lungs, kidneys, liver and brain, anti-inflammatory properties, anabolic effects on skeletal muscles and the ability to suppress bone density loss leading to osteoporosis. Ursolic acid also exhibits anti-microbial features against numerous strains of bacteria, HIV and HCV viruses and Plasmodium protozoa causing malaria.
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                Author and article information

                Contributors
                Tong Wang:
                ORCID: http://orcid.org/0000-0002-2111-7086
                twang1234@163.com
                Journal
                Journal ID (nlm-ta): Cancer Sci
                Journal ID (iso-abbrev): Cancer Sci
                Journal ID (doi): 10.1111/(ISSN)1349-7006
                Journal ID (publisher-id): CAS
                Title: Cancer Science
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Print): 1347-9032
                ISSN (Electronic): 1349-7006
                Publication date (Electronic): 18 November 2017
                Publication date (Print): January 2018
                Volume: 109
                Issue: 1 ( doiID: 10.1111/cas.2018.109.issue-1 )
                Pages: 94-102
                Affiliations
                [ 1 ] Department of Endoscopy Surgery Wuxi People's Hospital Affiliated to Nanjing Medical University Wuxi China
                Author notes
                [*] [* ] Correspondence

                Tong Wang, Department of Endoscopy Surgery, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, China.

                Email: twang1234@ 123456163.com

                Author information
                http://orcid.org/0000-0002-2111-7086
                Article
                Publisher ID: CAS13425
                DOI: 10.1111/cas.13425
                PMC ID: 5765292
                PubMed ID: 29034540
                SO-VID: 413a99eb-b12a-4305-addd-90dcdf6dcd8a
                Copyright © © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
                License:

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                Date received : 02 August 2017
                Date revision received : 09 October 2017
                Date accepted : 11 October 2017
                Page count
                Figures: 6, Tables: 3, Pages: 9, Words: 5317
                Funding
                Funded by: National Natural Sciences Foundation of China
                Award ID: 81371683/H1819
                Funded by: Clinical Medicine Project of Jiangsu Province
                Award ID: BL2014023
                Categories
                Subject: Original Article
                Subject: Original Articles
                Subject: Cell, Molecular, and Stem Cell Biology
                Custom metadata
                source-schema-version-number 2.0
                component-id cas13425
                cover-date January 2018
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_NLMPMC version:5.2.8 mode:remove_FC converted:12.01.2018

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: colorectal cancer,drug resistance,proliferation,reactive oxygen species,ursolic acid
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: colorectal cancer, drug resistance, proliferation, reactive oxygen species, ursolic acid

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