Apoptotic evaluation and cytotoxic effects of doxorubicin conjugated CaCO3-nanoparticles on breast cancer cell-line
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1
Laboratory of Molecular Biomedicine, Institute of Bioscience, University Putra Malaysia, Malaysia
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2
Faculty of Veterinary Medicine, Putra Malaysia University, Malaysia
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3
MAKNA Cancer Research, Institute of Bioscience, University Putra Malaysia, Malaysia
Background
Breast cancer is the most common malignant disease which is a serious burden to women worldwide. Aragonite calcium carbonate Nanoparticles loaded with doxorubicin (DOX) has recently emerged as an effective treatment of breast cancer. The aim of this study was to evaluate the efficacy of Doxorubicin-Calcium Carbonate Nanoparticles (DOX-Ar-CC-NPs) on MCF-7 breast cancer cells and to elucidate the mechanism of action, aiming at giving an insight on how DOX-Ar-CC-NPs influence chemo-resistivity and drug target delivery limiting undesirable side effects.
Methods
DOX-Ar-CC-NPs was synthesized using novel biomolecules from cheaply available natural seawater Cockle shells and characterized for particle geometry using electron microscopy. The anticancer activity of DOX-Ar-CC-NPs was determined using superoxide dismutase commercial ELISA kit for cell membrane integrity, flow cytometry, fluorescent imaging and electron microscopy for programmed cells death evaluation.
Results
Treatment of MCF-7 cells with DOX-Ar-CC-NPs and DOX showed a dose-dependent effect on cell viability. The DOX-loaded-Ar-CC-NPs had significant inhibitory effect on cell viability compared to DOX alone (p<0.05). Similar trend was noticed in cellular apoptosis, oxidative stress markers and cellular uptake evaluation. In addition, the results clearly showed that DOX-Ar-CC-NPs induced necrosis through endocytosis. However, treatment with DOX-Ar-CC-NPs significantly decreased the elevated level of superoxide dismutase 2 (SOD2) compared to untreated MCF-7 cells (control group). Furthermore, scanning electron micrographs revealed membrane blebbing and apoptotic bodies on DOX-Ar-CC-NPs treated cells, signifying that DOX-Ar-CC-NPs induces apoptosis in breast cancer cells.
Conclusion
Our findings revealed the ability of DOX-Ar-CC-NPs to induce apoptosis in MCF-7 cells, which indicates the high potency of the Ar-CC-NPs understudy in drug delivery.
Keywords:
Apoptosis,
MCF-7 cell lines,
Doxorubicin-Calcium Carbonate Nanoparticles,
Drug delivery,
Cytotoxicity
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:
Oral Presentation
Topic:
Cancer
Citation:
Ahmed
H,
Ajat
M,
Mansor
R,
Abdul Razak
I,
Danmaigoro
A,
Zubair Jaji
A,
Sani Mohammed
J and
Abu Bakar
M
(2019). Apoptotic evaluation and cytotoxic effects of doxorubicin conjugated 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.2018.63.00096
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Received:
19 Oct 2018;
Published Online:
17 Jan 2019.
*
Correspondence:
Prof. Md Zuki Abu Bakar, Faculty of Veterinary Medicine, Putra Malaysia University, Serdang, 43400, Malaysia, zuki@upm.edu.my