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Octreotide-periplocymarin conjugate prodrug for improving targetability and anti-tumor efficiency: synthesis, in vitro and in vivo evaluation
Cardiac glycosides could increase intracellular Ca(2+) ion by inhibiting the Na(+)/K(+)ATPase to induce apoptosis in many tumor cells. However, narrow therapeutic index, poor tumor selectivity and severe cardiovascular toxicity hinder their applications in cancer treatment. To improve the safety pro...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349917/ https://www.ncbi.nlm.nih.gov/pubmed/27861145 http://dx.doi.org/10.18632/oncotarget.13389 |
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author | Zhang, Hui-Yun Xu, Wen-Qian Zheng, Yuan-yuan Omari-Siaw, Emmanuel Zhu, Yuan Cao, Xia Tong, Shan-Shan Yu, Jiang-nan Xu, Xi-ming |
author_facet | Zhang, Hui-Yun Xu, Wen-Qian Zheng, Yuan-yuan Omari-Siaw, Emmanuel Zhu, Yuan Cao, Xia Tong, Shan-Shan Yu, Jiang-nan Xu, Xi-ming |
author_sort | Zhang, Hui-Yun |
collection | PubMed |
description | Cardiac glycosides could increase intracellular Ca(2+) ion by inhibiting the Na(+)/K(+)ATPase to induce apoptosis in many tumor cells. However, narrow therapeutic index, poor tumor selectivity and severe cardiovascular toxicity hinder their applications in cancer treatment. To improve the safety profile and tumor targetablility of cardiac glycosides, we designed octreotide conjugated periplocymarin, a cardiac glycoside isolated from Cortex periplocae. The conjugate showed higher cytotoxicity on MCF-7 cells and HepG2 tumor cells (SSTRs overexpression) but much less toxicity in L-02 normal cells. Tissue distribution studies of the conjugate using H(22) tumor model in mice showed higher accumulation in tumor and lower distribution in heart and liver than periplocymarin. Furthermore, in vivo anticancer effects of the conjugate on mice bearing H(22) cancer xenografts confirmed enhanced anti-tumor efficacy and decreased systemic toxicity. Altogether, octreotide-conjugated periplocymarin demonstrated tumor selectivity and may be useful as a targeting agent to improve the safety profile of cardiac glycosides for cancer therapy. |
format | Online Article Text |
id | pubmed-5349917 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53499172017-04-06 Octreotide-periplocymarin conjugate prodrug for improving targetability and anti-tumor efficiency: synthesis, in vitro and in vivo evaluation Zhang, Hui-Yun Xu, Wen-Qian Zheng, Yuan-yuan Omari-Siaw, Emmanuel Zhu, Yuan Cao, Xia Tong, Shan-Shan Yu, Jiang-nan Xu, Xi-ming Oncotarget Research Paper Cardiac glycosides could increase intracellular Ca(2+) ion by inhibiting the Na(+)/K(+)ATPase to induce apoptosis in many tumor cells. However, narrow therapeutic index, poor tumor selectivity and severe cardiovascular toxicity hinder their applications in cancer treatment. To improve the safety profile and tumor targetablility of cardiac glycosides, we designed octreotide conjugated periplocymarin, a cardiac glycoside isolated from Cortex periplocae. The conjugate showed higher cytotoxicity on MCF-7 cells and HepG2 tumor cells (SSTRs overexpression) but much less toxicity in L-02 normal cells. Tissue distribution studies of the conjugate using H(22) tumor model in mice showed higher accumulation in tumor and lower distribution in heart and liver than periplocymarin. Furthermore, in vivo anticancer effects of the conjugate on mice bearing H(22) cancer xenografts confirmed enhanced anti-tumor efficacy and decreased systemic toxicity. Altogether, octreotide-conjugated periplocymarin demonstrated tumor selectivity and may be useful as a targeting agent to improve the safety profile of cardiac glycosides for cancer therapy. Impact Journals LLC 2016-11-16 /pmc/articles/PMC5349917/ /pubmed/27861145 http://dx.doi.org/10.18632/oncotarget.13389 Text en Copyright: © 2016 Zhang 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Zhang, Hui-Yun Xu, Wen-Qian Zheng, Yuan-yuan Omari-Siaw, Emmanuel Zhu, Yuan Cao, Xia Tong, Shan-Shan Yu, Jiang-nan Xu, Xi-ming Octreotide-periplocymarin conjugate prodrug for improving targetability and anti-tumor efficiency: synthesis, in vitro and in vivo evaluation |
title | Octreotide-periplocymarin conjugate prodrug for improving targetability and anti-tumor efficiency: synthesis, in vitro and in vivo evaluation |
title_full | Octreotide-periplocymarin conjugate prodrug for improving targetability and anti-tumor efficiency: synthesis, in vitro and in vivo evaluation |
title_fullStr | Octreotide-periplocymarin conjugate prodrug for improving targetability and anti-tumor efficiency: synthesis, in vitro and in vivo evaluation |
title_full_unstemmed | Octreotide-periplocymarin conjugate prodrug for improving targetability and anti-tumor efficiency: synthesis, in vitro and in vivo evaluation |
title_short | Octreotide-periplocymarin conjugate prodrug for improving targetability and anti-tumor efficiency: synthesis, in vitro and in vivo evaluation |
title_sort | octreotide-periplocymarin conjugate prodrug for improving targetability and anti-tumor efficiency: synthesis, in vitro and in vivo evaluation |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349917/ https://www.ncbi.nlm.nih.gov/pubmed/27861145 http://dx.doi.org/10.18632/oncotarget.13389 |
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