A lethal synergy induced by phellinus linteus and camptothecin11 in colon cancer cells

Side effects of anti-cancer drugs are always challenging for effective cancer treatments. The polysaccharides extracted from Phellinus linteus (PLGL) have been widely used in treating cancers. However, the mechanism by which PLGL antagonizes cancerous growth has not been fully investigated. The curr...

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Autores principales: Yu, Tianqi, Ganapathy, Suthakar, Shen, Ling, Peng, Bo, Kim, Sung-Hoon, Makriyannis, Alexandros, Chen, Changyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814214/
https://www.ncbi.nlm.nih.gov/pubmed/29464074
http://dx.doi.org/10.18632/oncotarget.23918
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author Yu, Tianqi
Ganapathy, Suthakar
Shen, Ling
Peng, Bo
Kim, Sung-Hoon
Makriyannis, Alexandros
Chen, Changyan
author_facet Yu, Tianqi
Ganapathy, Suthakar
Shen, Ling
Peng, Bo
Kim, Sung-Hoon
Makriyannis, Alexandros
Chen, Changyan
author_sort Yu, Tianqi
collection PubMed
description Side effects of anti-cancer drugs are always challenging for effective cancer treatments. The polysaccharides extracted from Phellinus linteus (PLGL) have been widely used in treating cancers. However, the mechanism by which PLGL antagonizes cancerous growth has not been fully investigated. The current study demonstrated that human colon cancer HCT116 and HT29 cells became highly susceptible to cell death when being co-treated with PLGL and low dose of camptothecin11 (CPT11, a topoisomerase inhibitor-based drug), the efficacy of which was comparable as that generated by the high dose of CPT11. However, the co-treatment, unlike high doses of CPT11, was not cytotoxic to the control immortalized colon Caco-2 cells. The co-treatment caused high percentages of the colon cancer cells to accumulate in S phase of the cell cycle, which was also seen in the same cells received the high dose of CPT11 treatment. Chk1 was phosphorylated, and then rapidly degraded in the cancer cells treated with the high dose of CPT11 or co-treatment, but not in the cells treated with PLGL alone or low doses of CPT11. PLGL appeared enhancing CPT11 inhibitory effect on topoisomerase, and Chk1 degradatopm in the cancer cells. Furthermore, cyclin E (clnE) became unstable at the transcription level in co-treated or PLGL-treated colon cancer cells. The data suggested that PLGL functions in two ways to achieve its lethal synergy with CPT11 in colon cancer cells. Our findings are of potential significance as PLGL represents a promising medicine for overcoming the side effects of CPT11 and perhaps also for improving other CPTs-based regimens.
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spelling pubmed-58142142018-02-20 A lethal synergy induced by phellinus linteus and camptothecin11 in colon cancer cells Yu, Tianqi Ganapathy, Suthakar Shen, Ling Peng, Bo Kim, Sung-Hoon Makriyannis, Alexandros Chen, Changyan Oncotarget Research Paper Side effects of anti-cancer drugs are always challenging for effective cancer treatments. The polysaccharides extracted from Phellinus linteus (PLGL) have been widely used in treating cancers. However, the mechanism by which PLGL antagonizes cancerous growth has not been fully investigated. The current study demonstrated that human colon cancer HCT116 and HT29 cells became highly susceptible to cell death when being co-treated with PLGL and low dose of camptothecin11 (CPT11, a topoisomerase inhibitor-based drug), the efficacy of which was comparable as that generated by the high dose of CPT11. However, the co-treatment, unlike high doses of CPT11, was not cytotoxic to the control immortalized colon Caco-2 cells. The co-treatment caused high percentages of the colon cancer cells to accumulate in S phase of the cell cycle, which was also seen in the same cells received the high dose of CPT11 treatment. Chk1 was phosphorylated, and then rapidly degraded in the cancer cells treated with the high dose of CPT11 or co-treatment, but not in the cells treated with PLGL alone or low doses of CPT11. PLGL appeared enhancing CPT11 inhibitory effect on topoisomerase, and Chk1 degradatopm in the cancer cells. Furthermore, cyclin E (clnE) became unstable at the transcription level in co-treated or PLGL-treated colon cancer cells. The data suggested that PLGL functions in two ways to achieve its lethal synergy with CPT11 in colon cancer cells. Our findings are of potential significance as PLGL represents a promising medicine for overcoming the side effects of CPT11 and perhaps also for improving other CPTs-based regimens. Impact Journals LLC 2018-01-04 /pmc/articles/PMC5814214/ /pubmed/29464074 http://dx.doi.org/10.18632/oncotarget.23918 Text en Copyright: © 2018 Yu et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Yu, Tianqi
Ganapathy, Suthakar
Shen, Ling
Peng, Bo
Kim, Sung-Hoon
Makriyannis, Alexandros
Chen, Changyan
A lethal synergy induced by phellinus linteus and camptothecin11 in colon cancer cells
title A lethal synergy induced by phellinus linteus and camptothecin11 in colon cancer cells
title_full A lethal synergy induced by phellinus linteus and camptothecin11 in colon cancer cells
title_fullStr A lethal synergy induced by phellinus linteus and camptothecin11 in colon cancer cells
title_full_unstemmed A lethal synergy induced by phellinus linteus and camptothecin11 in colon cancer cells
title_short A lethal synergy induced by phellinus linteus and camptothecin11 in colon cancer cells
title_sort lethal synergy induced by phellinus linteus and camptothecin11 in colon cancer cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814214/
https://www.ncbi.nlm.nih.gov/pubmed/29464074
http://dx.doi.org/10.18632/oncotarget.23918
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