Ultrastructural Changes and Antitumor Effects of Doxorubicin/thymoquinone-loaded CaCO3 Nanoparticles on Breast Cancer Cell Line
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1
Institute of Bioscience, University Putra Malaysia, Malaysia
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2
Laboratory of Molecular Biomedicine, Institute of Bioscience, University Putra Malaysia, Malaysia
Ultrastructural Changes and Antitumor Effects of Doxorubicin/thymoquinone-loaded CaCO3 Nanoparticles on Breast Cancer Cell Line
Kehinde Muibat Ibiyeye 1, Norshariza Nurdin2, Mokrish Ajat3 and Abu Bakar Zakaria Zuki1,3
1Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti Putra Malaysia, Selangor, Malaysia
2Genetics and Regenerative Medicine Research Centre, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor, Malaysia
3Department of Veterinary Preclinical Sciences, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Selangor, Malaysia
The corresponding author: Abu Bakar Zakaria Zuki, zuki@upm.edu.my
Background
Combination chemotherapy of anticancer drugs is extensively being researched since it could reduce multidrug resistance and side effects as a result of lower dosage of each drug. In this study, we evaluated the effects of doxorubicin-loaded (Dox-ACNP), thymoquinone-loaded (TQ-ACNP) and a combined doxorubicin/thymoquinone-loaded cockle shell-derived aragonite calcium carbonate nanoparticles (Dox/TQ-ACNP) on breast cancer cell line and compared with their free drugs counterpart.
Methods
Cell viability using MTT assay, apoptosis with Annexin V-PI kit, morphological changes using contrast light microscope, scanning electron microscope and transmission electron microscope, cell cycle analysis, invasion assay and scratch assay were carried out. The cell viability was evaluated in breast cancer cell line (MDA MB231), normal breast cells (MDF10A) and normal fibroblast (3T3).
Results MDA MB231 IC50 dosage of drug-loaded nanoparticle was not toxic to the normal cells. This was confirmed by light microscopic assessment of cell morphology. The combination therapy showed enhanced apoptosis, reduction in cellular migration and invasion when compared to the single drug loaded nanoparticle and the free drugs. Scanning electron microscope showed presence of cell shrinkage, cell membrane blebbing, while transmission electron microscope showed nuclear fragmentation, disruption of cell membrane, apoptotic bodies, and disruption of mitochondrial cistern.
Conclusion The results from this study showed that the combined drug-loaded cockle shell-derived aragonite calcium carbonate nanoparticles (Dox/TQ-ACNP) showed higher efficacy in breast cancer cells at lower dose of doxorubicin or thymoquinone.
Keywords: Doxorubicin, Thymoquinone, Nanoparticle, Breast cancer
Keywords:
Doxorubicin,
Thymoquinone,
combination therapy,
nanoparticle,
breast cancer
Conference:
International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18)
“Seizing Opportunities and Addressing Challenges of Precision Medicine”, Putrajaya, Malaysia, 3 Dec - 5 Feb, 2019.
Presentation Type:
Poster Presentation
Topic:
Cancer
Citation:
Ibiyeye
KM and
Zuki
AZ
(2019). Ultrastructural Changes and Antitumor Effects of Doxorubicin/thymoquinone-loaded CaCO3 Nanoparticles on Breast Cancer Cell Line.
Front. Pharmacol.
Conference Abstract:
International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18)
“Seizing Opportunities and Addressing Challenges of Precision Medicine”.
doi: 10.3389/conf.fphar.2019.63.00018
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Received:
12 Oct 2018;
Published Online:
17 Jan 2019.
*
Correspondence:
Ms. Kehinde M Ibiyeye, Institute of Bioscience, University Putra Malaysia, Serdang, Malaysia, kehindebiyeye@gmail.com
Prof. Abu Bakar Z Zuki, Laboratory of Molecular Biomedicine, Institute of Bioscience, University Putra Malaysia, Serdang, Malaysia, zuki@upm.edu.my