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Optimized 2-methoxyestradiol invasomes fortified with apamin: a promising approach for suppression of A549 lung cancer cells
Certain anticancer agents selectively target the nucleus of cancer cells. One such drug is 2-methoxyestradiol (2ME), which is used for treating lung cancer. To improve the therapeutic effectiveness of these agents, many new methods have been devised. 2ME was entrapped into the core of hydrophobic in...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9154778/ https://www.ncbi.nlm.nih.gov/pubmed/35612292 http://dx.doi.org/10.1080/10717544.2022.2072412 |
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author | Awan, Zuhier A. AlGhamdi, Shareefa A. Alhakamy, Nabil A. Okbazghi, Solomon Z. Alfaleh, Mohamed A. Badr-Eldin, Shaimaa M. Aldawsari, Hibah M. Abourehab, Mohammed A. S. Asfour, Hani Z. Zakai, Shadi A. Alrabia, Mohammad W. Negm, Aya A. El-Moselhy, Mohamed A. Sharkawi, Sara S. Rizg, Waleed Y. |
author_facet | Awan, Zuhier A. AlGhamdi, Shareefa A. Alhakamy, Nabil A. Okbazghi, Solomon Z. Alfaleh, Mohamed A. Badr-Eldin, Shaimaa M. Aldawsari, Hibah M. Abourehab, Mohammed A. S. Asfour, Hani Z. Zakai, Shadi A. Alrabia, Mohammad W. Negm, Aya A. El-Moselhy, Mohamed A. Sharkawi, Sara S. Rizg, Waleed Y. |
author_sort | Awan, Zuhier A. |
collection | PubMed |
description | Certain anticancer agents selectively target the nucleus of cancer cells. One such drug is 2-methoxyestradiol (2ME), which is used for treating lung cancer. To improve the therapeutic effectiveness of these agents, many new methods have been devised. 2ME was entrapped into the core of hydrophobic invasomes (INVA) covered with Phospholipon 90G and apamin (APA). The Box–Behnken statistical design was implemented to enhance the composition. Using Design-Expert software (Stat-Ease Inc., Minneapolis, MN), the INVA component quantities were optimized to obtain spherical particles with the smallest size, that is, a diameter of 167.8 nm. 2ME-INVA-APA significantly inhibited A549 cells and exhibited IC(50) of 1.15 ± 0.04 µg/mL, which is lower than raw 2ME (IC(50) 5.6 ± 0.2 µg/mL). Post 2ME-INVA-APA administration, a significant rise in cell death and necrosis was seen among the A549 cells compared to those treated with plain formula or 2ME alone. This effect was indicated by increased Bax expression and reduced Bcl-2 expression, as well as mitochondrial membrane potential loss. Moreover, the cell cycle analysis showed that 2ME-INVA-APA arrests the G2-M phase of the A549 cells. Additionally, it was observed that the micellar formulation of the drug increased the cell count in pre-G1, thereby exhibiting phenomenal apoptotic potential. Furthermore, it up-regulates caspase-9 and p53 and downregulates TNF-α and NF-κβ. Collectively, these findings showed that our optimized 2ME-INVA-APA could easily seep through the cell membrane and induce apoptosis in relatively low doses. |
format | Online Article Text |
id | pubmed-9154778 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-91547782022-06-01 Optimized 2-methoxyestradiol invasomes fortified with apamin: a promising approach for suppression of A549 lung cancer cells Awan, Zuhier A. AlGhamdi, Shareefa A. Alhakamy, Nabil A. Okbazghi, Solomon Z. Alfaleh, Mohamed A. Badr-Eldin, Shaimaa M. Aldawsari, Hibah M. Abourehab, Mohammed A. S. Asfour, Hani Z. Zakai, Shadi A. Alrabia, Mohammad W. Negm, Aya A. El-Moselhy, Mohamed A. Sharkawi, Sara S. Rizg, Waleed Y. Drug Deliv Research Articles Certain anticancer agents selectively target the nucleus of cancer cells. One such drug is 2-methoxyestradiol (2ME), which is used for treating lung cancer. To improve the therapeutic effectiveness of these agents, many new methods have been devised. 2ME was entrapped into the core of hydrophobic invasomes (INVA) covered with Phospholipon 90G and apamin (APA). The Box–Behnken statistical design was implemented to enhance the composition. Using Design-Expert software (Stat-Ease Inc., Minneapolis, MN), the INVA component quantities were optimized to obtain spherical particles with the smallest size, that is, a diameter of 167.8 nm. 2ME-INVA-APA significantly inhibited A549 cells and exhibited IC(50) of 1.15 ± 0.04 µg/mL, which is lower than raw 2ME (IC(50) 5.6 ± 0.2 µg/mL). Post 2ME-INVA-APA administration, a significant rise in cell death and necrosis was seen among the A549 cells compared to those treated with plain formula or 2ME alone. This effect was indicated by increased Bax expression and reduced Bcl-2 expression, as well as mitochondrial membrane potential loss. Moreover, the cell cycle analysis showed that 2ME-INVA-APA arrests the G2-M phase of the A549 cells. Additionally, it was observed that the micellar formulation of the drug increased the cell count in pre-G1, thereby exhibiting phenomenal apoptotic potential. Furthermore, it up-regulates caspase-9 and p53 and downregulates TNF-α and NF-κβ. Collectively, these findings showed that our optimized 2ME-INVA-APA could easily seep through the cell membrane and induce apoptosis in relatively low doses. Taylor & Francis 2022-05-25 /pmc/articles/PMC9154778/ /pubmed/35612292 http://dx.doi.org/10.1080/10717544.2022.2072412 Text en © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Awan, Zuhier A. AlGhamdi, Shareefa A. Alhakamy, Nabil A. Okbazghi, Solomon Z. Alfaleh, Mohamed A. Badr-Eldin, Shaimaa M. Aldawsari, Hibah M. Abourehab, Mohammed A. S. Asfour, Hani Z. Zakai, Shadi A. Alrabia, Mohammad W. Negm, Aya A. El-Moselhy, Mohamed A. Sharkawi, Sara S. Rizg, Waleed Y. Optimized 2-methoxyestradiol invasomes fortified with apamin: a promising approach for suppression of A549 lung cancer cells |
title | Optimized 2-methoxyestradiol invasomes fortified with apamin: a promising approach for suppression of A549 lung cancer cells |
title_full | Optimized 2-methoxyestradiol invasomes fortified with apamin: a promising approach for suppression of A549 lung cancer cells |
title_fullStr | Optimized 2-methoxyestradiol invasomes fortified with apamin: a promising approach for suppression of A549 lung cancer cells |
title_full_unstemmed | Optimized 2-methoxyestradiol invasomes fortified with apamin: a promising approach for suppression of A549 lung cancer cells |
title_short | Optimized 2-methoxyestradiol invasomes fortified with apamin: a promising approach for suppression of A549 lung cancer cells |
title_sort | optimized 2-methoxyestradiol invasomes fortified with apamin: a promising approach for suppression of a549 lung cancer cells |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9154778/ https://www.ncbi.nlm.nih.gov/pubmed/35612292 http://dx.doi.org/10.1080/10717544.2022.2072412 |
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