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2017 ; 12
(ä): 6503-6520
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Combination of palladium nanoparticles and tubastatin-A potentiates apoptosis in
human breast cancer cells: a novel therapeutic approach for cancer
#MMPMID28919751
Yuan YG
; Peng QL
; Gurunathan S
Int J Nanomedicine
2017[]; 12
(ä): 6503-6520
PMID28919751
show ga
BACKGROUND: Breast cancer is the most common malignant disease that occurs in
women. Histone deacetylase (HDAC) inhibition has recently emerged as an effective
and attractive target for the treatment of cancer. The aim of this study was to
investigate the efficacy of a combined treatment of tubastatin A (TUB-A) and
palladium nanoparticles (PdNPs) against MDA-MB-231 human breast cancer cells
using two different cytotoxic agents that work by two different mechanisms,
thereby decreasing the probability of chemoresistance in cancer cells and
increasing the efficacy of toxicity, to provide efficient therapy for advanced
stage of cancer without any undesired side effects. METHODS: PdNPs were
synthesized using a novel biomolecule called R-phycoerythrin and characterized
using various analytical techniques. The combinatorial effect of TUB-A and PdNPs
was assessed by various cellular and biochemical assays and also by gene
expression analysis. RESULTS: The biologically synthesized PdNPs had an average
size of 25 nm and were spherical in shape. Treatment of MDA-MB-231 human breast
cancer cells with TUB-A or PdNPs showed a dose-dependent effect on cell
viability. The combination of 4 ?M TUB-A and 4 ?M PdNPs had a significant
inhibitory effect on cell viability compared with either TUB-A or PdNPs alone.
The combinatorial treatment also had a more pronounced effect on the inhibition
of HDAC activity and enhanced apoptosis by regulating various cellular and
biochemical changes. CONCLUSION: Our results suggest that there was a strong
synergistic interaction between TUB-A and PdNPs in increasing apoptosis in human
breast cancer cells. These data provide an important preclinical basis for future
clinical trials on this drug combination. This combinatorial treatment increased
therapeutic potentials, thereby demonstrating a relevant targeted therapy for
breast cancer. Furthermore, we have provided the first evidence for the
combinatorial effect and mechanism of toxicity of TUB-A and PdNPs in human breast
cancer cells. The novelties of the study were identification of a combination
therapy that consists of suitable therapeutic molecules that kill cancer cells
and also exploration of two different possible mechanisms involved to reduce
chemoresistance in cancer cells.