Protective Effect of Polysaccharides Extracted from Cudrania tricuspidata Fruit against Cisplatin-Induced Cytotoxicity in Macrophages and a Mouse Model
Although cisplatin is one of most effective chemotherapeutic drugs that is widely used to treat various types of cancer, it can cause undesirable damage in immune cells and normal tissue because of its strong cytotoxicity and non-selectivity. This study was conducted to investigate the cytoprotectiv...
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| Veröffentlicht in: | International journal of molecular sciences 2021-07, Vol.22 (14), p.7512, Article 7512 |
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| description | Although cisplatin is one of most effective chemotherapeutic drugs that is widely used to treat various types of cancer, it can cause undesirable damage in immune cells and normal tissue because of its strong cytotoxicity and non-selectivity. This study was conducted to investigate the cytoprotective effects of Cudrania tricuspidata fruit-derived polysaccharides (CTPS) against cisplatin-induced cytotoxicity in macrophages, lung cancer cell lines, and a mouse model, and to explore the possibility of application of CTPS as a supplement for anticancer therapy. Both cisplatin alone and cisplatin with CTPS induced a significant cytotoxicity in A549 and H460 lung cancer cells, whereas cytotoxicity was suppressed by CTPS in cisplatin-treated RAW264.7 cells. CTPS significantly attenuated the apoptotic and necrotic population, as well as cell penetration in cisplatin-treated RAW264.7 cells, which ultimately inhibited the upregulation of Bcl-2-associated X protein (Bax), cytosolic cytochrome c, poly (adenosine diphosphateribose) polymerase (PARP) cleavage, and caspases-3, -8, and -9, and the downregulation of B cell lymphoma-2 (Bcl-2). The CTPS-induced cytoprotective action was mediated with a reduction in reactive oxygen species production and mitochondrial transmembrane potential loss in cisplatin-treated RAW264.7 cells. In agreement with the results obtained above, CTPS induced the attenuation of cell damage in cisplatin-treated bone marrow-derived macrophages (primary cells). In in vivo studies, CTPS significantly inhibited metastatic colonies and bodyweight loss as well as immunotoxicity in splenic T cells compared to the cisplatin-treated group in lung metastasis-induced mice. Furthermore, CTPS decreased the level of CRE and BUN in serum. In summation, these results suggest that CTPS-induced cytoprotective action may play a role in alleviating the side effects induced by chemotherapeutic drugs. |
| doi_str_mv | 10.3390/ijms22147512 |
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This study was conducted to investigate the cytoprotective effects of Cudrania tricuspidata fruit-derived polysaccharides (CTPS) against cisplatin-induced cytotoxicity in macrophages, lung cancer cell lines, and a mouse model, and to explore the possibility of application of CTPS as a supplement for anticancer therapy. Both cisplatin alone and cisplatin with CTPS induced a significant cytotoxicity in A549 and H460 lung cancer cells, whereas cytotoxicity was suppressed by CTPS in cisplatin-treated RAW264.7 cells. CTPS significantly attenuated the apoptotic and necrotic population, as well as cell penetration in cisplatin-treated RAW264.7 cells, which ultimately inhibited the upregulation of Bcl-2-associated X protein (Bax), cytosolic cytochrome c, poly (adenosine diphosphateribose) polymerase (PARP) cleavage, and caspases-3, -8, and -9, and the downregulation of B cell lymphoma-2 (Bcl-2). The CTPS-induced cytoprotective action was mediated with a reduction in reactive oxygen species production and mitochondrial transmembrane potential loss in cisplatin-treated RAW264.7 cells. In agreement with the results obtained above, CTPS induced the attenuation of cell damage in cisplatin-treated bone marrow-derived macrophages (primary cells). In in vivo studies, CTPS significantly inhibited metastatic colonies and bodyweight loss as well as immunotoxicity in splenic T cells compared to the cisplatin-treated group in lung metastasis-induced mice. Furthermore, CTPS decreased the level of CRE and BUN in serum. In summation, these results suggest that CTPS-induced cytoprotective action may play a role in alleviating the side effects induced by chemotherapeutic drugs.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms22147512</identifier><identifier>PMID: 34299130</identifier><language>eng</language><publisher>BASEL: Mdpi</publisher><subject>Adenosine ; Apoptosis ; Attenuation ; BAX protein ; Bcl-2 protein ; Bcl-x protein ; Biochemistry & Molecular Biology ; Biocompatibility ; Bone marrow ; cancer cisplatin ; Cancer therapies ; Chemistry ; Chemistry, Multidisciplinary ; Chemotherapy ; Cisplatin ; Cudrania tricuspidata ; Cytochrome ; Cytochrome c ; cytoprotective action ; Cytotoxicity ; Drugs ; Immune system ; Immunosuppressive agents ; Immunotoxicity ; In vivo methods and tests ; Life Sciences & Biomedicine ; Lung cancer ; Lymphocytes ; Lymphocytes T ; macrophage ; Macrophages ; Membrane potential ; Metastases ; Metastasis ; Mitochondria ; Morphology ; Natural products ; Physical Sciences ; Poly(ADP-ribose) polymerase ; Polysaccharides ; Science & Technology ; Selectivity ; Spleen ; Tumor cell lines</subject><ispartof>International journal of molecular sciences, 2021-07, Vol.22 (14), p.7512, Article 7512</ispartof><rights>2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>4</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000677367700001</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c455t-4460e5bf3807c638b008e080ccb577bfa1f9fc40ef5e3ab80100965951d5fd3c3</citedby><cites>FETCH-LOGICAL-c455t-4460e5bf3807c638b008e080ccb577bfa1f9fc40ef5e3ab80100965951d5fd3c3</cites><orcidid>0000-0002-7103-1344</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304288/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304288/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,886,27928,27929,53795,53797</link.rule.ids></links><search><creatorcontrib>Byun, Eui-Baek</creatorcontrib><creatorcontrib>Song, Ha-Yeon</creatorcontrib><creatorcontrib>Kim, Woo Sik</creatorcontrib><creatorcontrib>Han, Jeong Moo</creatorcontrib><creatorcontrib>Seo, Ho Seong</creatorcontrib><creatorcontrib>Park, Sang-Hyun</creatorcontrib><creatorcontrib>Kim, Kwangwook</creatorcontrib><creatorcontrib>Byun, Eui-Hong</creatorcontrib><title>Protective Effect of Polysaccharides Extracted from Cudrania tricuspidata Fruit against Cisplatin-Induced Cytotoxicity in Macrophages and a Mouse Model</title><title>International journal of molecular sciences</title><addtitle>INT J MOL SCI</addtitle><description>Although cisplatin is one of most effective chemotherapeutic drugs that is widely used to treat various types of cancer, it can cause undesirable damage in immune cells and normal tissue because of its strong cytotoxicity and non-selectivity. This study was conducted to investigate the cytoprotective effects of Cudrania tricuspidata fruit-derived polysaccharides (CTPS) against cisplatin-induced cytotoxicity in macrophages, lung cancer cell lines, and a mouse model, and to explore the possibility of application of CTPS as a supplement for anticancer therapy. Both cisplatin alone and cisplatin with CTPS induced a significant cytotoxicity in A549 and H460 lung cancer cells, whereas cytotoxicity was suppressed by CTPS in cisplatin-treated RAW264.7 cells. CTPS significantly attenuated the apoptotic and necrotic population, as well as cell penetration in cisplatin-treated RAW264.7 cells, which ultimately inhibited the upregulation of Bcl-2-associated X protein (Bax), cytosolic cytochrome c, poly (adenosine diphosphateribose) polymerase (PARP) cleavage, and caspases-3, -8, and -9, and the downregulation of B cell lymphoma-2 (Bcl-2). The CTPS-induced cytoprotective action was mediated with a reduction in reactive oxygen species production and mitochondrial transmembrane potential loss in cisplatin-treated RAW264.7 cells. In agreement with the results obtained above, CTPS induced the attenuation of cell damage in cisplatin-treated bone marrow-derived macrophages (primary cells). In in vivo studies, CTPS significantly inhibited metastatic colonies and bodyweight loss as well as immunotoxicity in splenic T cells compared to the cisplatin-treated group in lung metastasis-induced mice. Furthermore, CTPS decreased the level of CRE and BUN in serum. In summation, these results suggest that CTPS-induced cytoprotective action may play a role in alleviating the side effects induced by chemotherapeutic drugs.</description><subject>Adenosine</subject><subject>Apoptosis</subject><subject>Attenuation</subject><subject>BAX protein</subject><subject>Bcl-2 protein</subject><subject>Bcl-x protein</subject><subject>Biochemistry & Molecular Biology</subject><subject>Biocompatibility</subject><subject>Bone marrow</subject><subject>cancer cisplatin</subject><subject>Cancer therapies</subject><subject>Chemistry</subject><subject>Chemistry, Multidisciplinary</subject><subject>Chemotherapy</subject><subject>Cisplatin</subject><subject>Cudrania tricuspidata</subject><subject>Cytochrome</subject><subject>Cytochrome c</subject><subject>cytoprotective action</subject><subject>Cytotoxicity</subject><subject>Drugs</subject><subject>Immune system</subject><subject>Immunosuppressive agents</subject><subject>Immunotoxicity</subject><subject>In vivo methods 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Mouse Model</title><author>Byun, Eui-Baek ; Song, Ha-Yeon ; Kim, Woo Sik ; Han, Jeong Moo ; Seo, Ho Seong ; Park, Sang-Hyun ; Kim, Kwangwook ; Byun, Eui-Hong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-4460e5bf3807c638b008e080ccb577bfa1f9fc40ef5e3ab80100965951d5fd3c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adenosine</topic><topic>Apoptosis</topic><topic>Attenuation</topic><topic>BAX protein</topic><topic>Bcl-2 protein</topic><topic>Bcl-x protein</topic><topic>Biochemistry & Molecular Biology</topic><topic>Biocompatibility</topic><topic>Bone marrow</topic><topic>cancer cisplatin</topic><topic>Cancer therapies</topic><topic>Chemistry</topic><topic>Chemistry, Multidisciplinary</topic><topic>Chemotherapy</topic><topic>Cisplatin</topic><topic>Cudrania tricuspidata</topic><topic>Cytochrome</topic><topic>Cytochrome c</topic><topic>cytoprotective 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SCI</stitle><date>2021-07-13</date><risdate>2021</risdate><volume>22</volume><issue>14</issue><spage>7512</spage><pages>7512-</pages><artnum>7512</artnum><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Although cisplatin is one of most effective chemotherapeutic drugs that is widely used to treat various types of cancer, it can cause undesirable damage in immune cells and normal tissue because of its strong cytotoxicity and non-selectivity. This study was conducted to investigate the cytoprotective effects of Cudrania tricuspidata fruit-derived polysaccharides (CTPS) against cisplatin-induced cytotoxicity in macrophages, lung cancer cell lines, and a mouse model, and to explore the possibility of application of CTPS as a supplement for anticancer therapy. Both cisplatin alone and cisplatin with CTPS induced a significant cytotoxicity in A549 and H460 lung cancer cells, whereas cytotoxicity was suppressed by CTPS in cisplatin-treated RAW264.7 cells. CTPS significantly attenuated the apoptotic and necrotic population, as well as cell penetration in cisplatin-treated RAW264.7 cells, which ultimately inhibited the upregulation of Bcl-2-associated X protein (Bax), cytosolic cytochrome c, poly (adenosine diphosphateribose) polymerase (PARP) cleavage, and caspases-3, -8, and -9, and the downregulation of B cell lymphoma-2 (Bcl-2). The CTPS-induced cytoprotective action was mediated with a reduction in reactive oxygen species production and mitochondrial transmembrane potential loss in cisplatin-treated RAW264.7 cells. In agreement with the results obtained above, CTPS induced the attenuation of cell damage in cisplatin-treated bone marrow-derived macrophages (primary cells). In in vivo studies, CTPS significantly inhibited metastatic colonies and bodyweight loss as well as immunotoxicity in splenic T cells compared to the cisplatin-treated group in lung metastasis-induced mice. Furthermore, CTPS decreased the level of CRE and BUN in serum. In summation, these results suggest that CTPS-induced cytoprotective action may play a role in alleviating the side effects induced by chemotherapeutic drugs.</abstract><cop>BASEL</cop><pub>Mdpi</pub><pmid>34299130</pmid><doi>10.3390/ijms22147512</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0002-7103-1344</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adenosine Apoptosis Attenuation BAX protein Bcl-2 protein Bcl-x protein Biochemistry & Molecular Biology Biocompatibility Bone marrow cancer cisplatin Cancer therapies Chemistry Chemistry, Multidisciplinary Chemotherapy Cisplatin Cudrania tricuspidata Cytochrome Cytochrome c cytoprotective action Cytotoxicity Drugs Immune system Immunosuppressive agents Immunotoxicity In vivo methods and tests Life Sciences & Biomedicine Lung cancer Lymphocytes Lymphocytes T macrophage Macrophages Membrane potential Metastases Metastasis Mitochondria Morphology Natural products Physical Sciences Poly(ADP-ribose) polymerase Polysaccharides Science & Technology Selectivity Spleen Tumor cell lines |
| title | Protective Effect of Polysaccharides Extracted from Cudrania tricuspidata Fruit against Cisplatin-Induced Cytotoxicity in Macrophages and a Mouse Model |
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