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Platinum-Based Drugs Differentially Affect the Ultrastructure of Breast Cancer Cell Types

Breast cancer (BC) is the most common cause of cancer-related death worldwide. Although platinum-based drugs (PBDs) are effective anticancer agents, responsive patients eventually become resistant. While resistance of some cancers to PBDs has been explored, the cellular responses of BC cells are not...

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Autores principales: Al-Bahlani, Shadia, Al-Dhahli, Buthaina, Al-Adawi, Kawther, Al-Nabhani, Abdurahman, Al-Kindi, Mohamed
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5362716/
https://www.ncbi.nlm.nih.gov/pubmed/28377926
http://dx.doi.org/10.1155/2017/3178794
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author Al-Bahlani, Shadia
Al-Dhahli, Buthaina
Al-Adawi, Kawther
Al-Nabhani, Abdurahman
Al-Kindi, Mohamed
author_facet Al-Bahlani, Shadia
Al-Dhahli, Buthaina
Al-Adawi, Kawther
Al-Nabhani, Abdurahman
Al-Kindi, Mohamed
author_sort Al-Bahlani, Shadia
collection PubMed
description Breast cancer (BC) is the most common cause of cancer-related death worldwide. Although platinum-based drugs (PBDs) are effective anticancer agents, responsive patients eventually become resistant. While resistance of some cancers to PBDs has been explored, the cellular responses of BC cells are not studied yet. Therefore, we aim to assess the differential effects of PBDs on BC ultrastructure. Three representative cells were treated with different concentrations and timing of Cisplatin, Carboplatin, and Oxaliplatin. Changes on cell surface and ultrastructure were detected by scanning (SEM) and transmission electron microscope (TEM). In SEM, control cells were semiflattened containing microvilli with extending lamellipodia while treated ones were round with irregular surface and several pores, indicating drug entry. Prolonged treatment resembled distinct apoptotic features such as shrinkage, membrane blebs, and narrowing of lamellipodia with blunt microvilli. TEM detected PBDs' deposits that scattered among cellular organelles inducing structural distortion, lumen swelling, chromatin condensation, and nuclear fragmentation. Deposits were attracted to fat droplets, explained by drug hydrophobic properties, while later they were located close to cell membrane, suggesting drug efflux. Phagosomes with destructed organelles and deposits were detected as defending mechanism. Understanding BC cells response to PBDs might provide new insight for an effective treatment.
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spelling pubmed-53627162017-04-04 Platinum-Based Drugs Differentially Affect the Ultrastructure of Breast Cancer Cell Types Al-Bahlani, Shadia Al-Dhahli, Buthaina Al-Adawi, Kawther Al-Nabhani, Abdurahman Al-Kindi, Mohamed Biomed Res Int Research Article Breast cancer (BC) is the most common cause of cancer-related death worldwide. Although platinum-based drugs (PBDs) are effective anticancer agents, responsive patients eventually become resistant. While resistance of some cancers to PBDs has been explored, the cellular responses of BC cells are not studied yet. Therefore, we aim to assess the differential effects of PBDs on BC ultrastructure. Three representative cells were treated with different concentrations and timing of Cisplatin, Carboplatin, and Oxaliplatin. Changes on cell surface and ultrastructure were detected by scanning (SEM) and transmission electron microscope (TEM). In SEM, control cells were semiflattened containing microvilli with extending lamellipodia while treated ones were round with irregular surface and several pores, indicating drug entry. Prolonged treatment resembled distinct apoptotic features such as shrinkage, membrane blebs, and narrowing of lamellipodia with blunt microvilli. TEM detected PBDs' deposits that scattered among cellular organelles inducing structural distortion, lumen swelling, chromatin condensation, and nuclear fragmentation. Deposits were attracted to fat droplets, explained by drug hydrophobic properties, while later they were located close to cell membrane, suggesting drug efflux. Phagosomes with destructed organelles and deposits were detected as defending mechanism. Understanding BC cells response to PBDs might provide new insight for an effective treatment. Hindawi 2017 2017-03-09 /pmc/articles/PMC5362716/ /pubmed/28377926 http://dx.doi.org/10.1155/2017/3178794 Text en Copyright © 2017 Shadia Al-Bahlani et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Al-Bahlani, Shadia
Al-Dhahli, Buthaina
Al-Adawi, Kawther
Al-Nabhani, Abdurahman
Al-Kindi, Mohamed
Platinum-Based Drugs Differentially Affect the Ultrastructure of Breast Cancer Cell Types
title Platinum-Based Drugs Differentially Affect the Ultrastructure of Breast Cancer Cell Types
title_full Platinum-Based Drugs Differentially Affect the Ultrastructure of Breast Cancer Cell Types
title_fullStr Platinum-Based Drugs Differentially Affect the Ultrastructure of Breast Cancer Cell Types
title_full_unstemmed Platinum-Based Drugs Differentially Affect the Ultrastructure of Breast Cancer Cell Types
title_short Platinum-Based Drugs Differentially Affect the Ultrastructure of Breast Cancer Cell Types
title_sort platinum-based drugs differentially affect the ultrastructure of breast cancer cell types
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5362716/
https://www.ncbi.nlm.nih.gov/pubmed/28377926
http://dx.doi.org/10.1155/2017/3178794
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