Abstract
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 dosages of drug-loaded nanoparticle were not toxic to the normal cells. 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 and thymoquinone.
Highlights
In the last few decades, combination therapy has been more reliable than mono-therapies because cancer cells possess survival multiple pathways including uncontrolled proliferation, evasion of apoptosis, stimulation of angiogenesis and propensity for local invasion and distance metastases [1]
Nanotechnology has shown a great advantage in drug delivery for cancer treatment by enhancing buildup of cytotoxics in tumor tissue, specificity in tumor targeting, reducing the cytotoxics side effect on normal cells, reducing systemic side effect, increasing drug solubility, and increasing maximum tolerated dose [3, 4]
The cell viability studies were evaluated on MDA-MB-231 breast cancer cells using an MTT assay
Summary
In the last few decades, combination therapy has been more reliable than mono-therapies because cancer cells possess survival multiple pathways including uncontrolled proliferation, evasion of apoptosis, stimulation of angiogenesis and propensity for local invasion and distance metastases [1]. Combination chemotherapy comprising of two or more anticancer drugs has been shown to reduce drug resistance and side effects due to lower dosage of each drug [3]. Nanotechnology has shown a great advantage in drug delivery for cancer treatment by enhancing buildup of cytotoxics in tumor tissue, specificity in tumor targeting, reducing the cytotoxics side effect on normal cells, reducing systemic side effect, increasing drug solubility, and increasing maximum tolerated dose [3, 4]. Calcium carbonate (CaCO3) nanoparticles has got immense attention because it is the most biocompatible; this makes aragonite an excellent biological drug delivery systems of anticancer drugs [5, 6]. 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. 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
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
