{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T01:10:34Z","timestamp":1787965834850,"version":"build-2784847793"},"reference-count":47,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T00:00:00Z","timestamp":1626134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2019R1C1C1002484"],"award-info":[{"award-number":["2019R1C1C1002484"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2019R1F1A1061378"],"award-info":[{"award-number":["2019R1F1A1061378"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Nuclear R&amp;D Program of Ministry of Science","award":["No grant number"],"award-info":[{"award-number":["No grant number"]}]},{"DOI":"10.13039\/501100002510","name":"Kongju National University","doi-asserted-by":"publisher","award":["2020-0178-01"],"award-info":[{"award-number":["2020-0178-01"]}],"id":[{"id":"10.13039\/501100002510","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms22147512","type":"journal-article","created":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T22:25:31Z","timestamp":1626215131000},"page":"7512","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Protective Effect of Polysaccharides Extracted from Cudrania tricuspidata Fruit against Cisplatin-Induced Cytotoxicity in Macrophages and a Mouse Model"],"prefix":"10.3390","volume":"22","author":[{"given":"Eui-Baek","family":"Byun","sequence":"first","affiliation":[{"name":"Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 56212, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ha-Yeon","family":"Song","sequence":"additional","affiliation":[{"name":"Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 56212, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woo Sik","family":"Kim","sequence":"additional","affiliation":[{"name":"Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 56212, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong Moo","family":"Han","sequence":"additional","affiliation":[{"name":"Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 56212, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7103-1344","authenticated-orcid":false,"given":"Ho Seong","family":"Seo","sequence":"additional","affiliation":[{"name":"Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 56212, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Hyun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Food Science and Technology, Kongju National University, Yesan 32439, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwangwook","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Food Science and Technology, Kongju National University, Yesan 32439, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eui-Hong","family":"Byun","sequence":"additional","affiliation":[{"name":"Department of Food Science and Technology, Kongju National University, Yesan 32439, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,13]]},"reference":[{"key":"ref_1","first-page":"2058","article-title":"Cardiotoxicity of Cancer Chemotherapy\u2014Mechanisms and Therapeutic Approach","volume":"44","author":"Akazawa","year":"2017","journal-title":"Gan Kagaku Ryoho Cancer Chemother."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/S0140-6736(13)62224-2","article-title":"Global cancer patterns: Causes and prevention","volume":"383","author":"Vineis","year":"2014","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5258","DOI":"10.1073\/pnas.92.12.5258","article-title":"The Causes and Prevention of Cancer","volume":"92","author":"Ames","year":"1995","journal-title":"Proc. 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