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Crosslink among phosphatidylinositol-3 kinase/Akt, PTEN and STAT-5A signaling pathways post liposomal galactomannan hepatocellular carcinoma therapy
Liposomal drug-delivery systems (LDDs) provide a promising opportunity to precisely target organs, improve drug bioavailability and reduce systemic toxicity. On the other hand, PI(3)K/Akt signaling pathways control various intracellular functions including apoptosis, invasion and cell growth. Hyper...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683274/ https://www.ncbi.nlm.nih.gov/pubmed/33251120 http://dx.doi.org/10.1016/j.toxrep.2020.10.018 |
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author | Abdel-Megeed, Rehab M. Abd El-Alim, Sameh H. Arafa, Azza F. Matloub, Azza A. Farrag, Abd El Razik H Darwish, Asmaa B. Abdel- Hamid, Abdel- Hamid Z. Kadry, Mai O. |
author_facet | Abdel-Megeed, Rehab M. Abd El-Alim, Sameh H. Arafa, Azza F. Matloub, Azza A. Farrag, Abd El Razik H Darwish, Asmaa B. Abdel- Hamid, Abdel- Hamid Z. Kadry, Mai O. |
author_sort | Abdel-Megeed, Rehab M. |
collection | PubMed |
description | Liposomal drug-delivery systems (LDDs) provide a promising opportunity to precisely target organs, improve drug bioavailability and reduce systemic toxicity. On the other hand, PI(3)K/Akt signaling pathways control various intracellular functions including apoptosis, invasion and cell growth. Hyper activation of PI3K and Akt is detected in some types of cancer that posses defect in PTEN. Tracking the crosstalk between PI3K/Akt, PTEN and STAT 5A signaling pathways, in cancer could result in identifying new therapeutic agents. The current study, identified an over view on PI3K/Akt, PTEN and STAT-5A networks, in addition to their biological roles in hepatocellular carcinoma (HCC). In the current study galactomannan was extracted from Caesalpinia gilliesii seeds then loaded in liposomes. Liposomes were prepared employing phosphatidyl choline and different concentrations of cholesterol. HCC was then induced in Wistar albino rats followed by liposomal galactomannan (700 ± 100 nm) treatment. Liver enzymes as well as antioxidants were assessed and PI3K/Akt, PTEN and STAT-5A gene expression were investigated. The prepared vesicles revealed entrapment efficiencies ranging from 23.55 to 69.17%, and negative zeta potential values. The optimum formulation revealed spherical morphology as well as diffusion controlled in vitro release pattern. Liposomal galactomannan elucidated a significant reduction in liver enzymes and MDA as well as PI3K/Akt, PTEN and STAT 5A gene expression. A significant elevation in GST and GSH were deduced. In conclusion, Liposomal galactomannan revealed a promising candidate for HCC therapy. |
format | Online Article Text |
id | pubmed-7683274 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-76832742020-11-27 Crosslink among phosphatidylinositol-3 kinase/Akt, PTEN and STAT-5A signaling pathways post liposomal galactomannan hepatocellular carcinoma therapy Abdel-Megeed, Rehab M. Abd El-Alim, Sameh H. Arafa, Azza F. Matloub, Azza A. Farrag, Abd El Razik H Darwish, Asmaa B. Abdel- Hamid, Abdel- Hamid Z. Kadry, Mai O. Toxicol Rep Regular Article Liposomal drug-delivery systems (LDDs) provide a promising opportunity to precisely target organs, improve drug bioavailability and reduce systemic toxicity. On the other hand, PI(3)K/Akt signaling pathways control various intracellular functions including apoptosis, invasion and cell growth. Hyper activation of PI3K and Akt is detected in some types of cancer that posses defect in PTEN. Tracking the crosstalk between PI3K/Akt, PTEN and STAT 5A signaling pathways, in cancer could result in identifying new therapeutic agents. The current study, identified an over view on PI3K/Akt, PTEN and STAT-5A networks, in addition to their biological roles in hepatocellular carcinoma (HCC). In the current study galactomannan was extracted from Caesalpinia gilliesii seeds then loaded in liposomes. Liposomes were prepared employing phosphatidyl choline and different concentrations of cholesterol. HCC was then induced in Wistar albino rats followed by liposomal galactomannan (700 ± 100 nm) treatment. Liver enzymes as well as antioxidants were assessed and PI3K/Akt, PTEN and STAT-5A gene expression were investigated. The prepared vesicles revealed entrapment efficiencies ranging from 23.55 to 69.17%, and negative zeta potential values. The optimum formulation revealed spherical morphology as well as diffusion controlled in vitro release pattern. Liposomal galactomannan elucidated a significant reduction in liver enzymes and MDA as well as PI3K/Akt, PTEN and STAT 5A gene expression. A significant elevation in GST and GSH were deduced. In conclusion, Liposomal galactomannan revealed a promising candidate for HCC therapy. Elsevier 2020-11-05 /pmc/articles/PMC7683274/ /pubmed/33251120 http://dx.doi.org/10.1016/j.toxrep.2020.10.018 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Regular Article Abdel-Megeed, Rehab M. Abd El-Alim, Sameh H. Arafa, Azza F. Matloub, Azza A. Farrag, Abd El Razik H Darwish, Asmaa B. Abdel- Hamid, Abdel- Hamid Z. Kadry, Mai O. Crosslink among phosphatidylinositol-3 kinase/Akt, PTEN and STAT-5A signaling pathways post liposomal galactomannan hepatocellular carcinoma therapy |
title | Crosslink among phosphatidylinositol-3 kinase/Akt, PTEN and STAT-5A signaling pathways post liposomal galactomannan hepatocellular carcinoma therapy |
title_full | Crosslink among phosphatidylinositol-3 kinase/Akt, PTEN and STAT-5A signaling pathways post liposomal galactomannan hepatocellular carcinoma therapy |
title_fullStr | Crosslink among phosphatidylinositol-3 kinase/Akt, PTEN and STAT-5A signaling pathways post liposomal galactomannan hepatocellular carcinoma therapy |
title_full_unstemmed | Crosslink among phosphatidylinositol-3 kinase/Akt, PTEN and STAT-5A signaling pathways post liposomal galactomannan hepatocellular carcinoma therapy |
title_short | Crosslink among phosphatidylinositol-3 kinase/Akt, PTEN and STAT-5A signaling pathways post liposomal galactomannan hepatocellular carcinoma therapy |
title_sort | crosslink among phosphatidylinositol-3 kinase/akt, pten and stat-5a signaling pathways post liposomal galactomannan hepatocellular carcinoma therapy |
topic | Regular Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683274/ https://www.ncbi.nlm.nih.gov/pubmed/33251120 http://dx.doi.org/10.1016/j.toxrep.2020.10.018 |
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