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Nano-hole induction by nanodiamond and nanoplatinum liquid, DPV576, reverses multidrug resistance in human myeloid leukemia (HL60/AR).

Ghoneum A, Sharma S, Gimzewski J - Int J Nanomedicine (2013)

Bottom Line: Co-treatment of HL60/AR cells with DNR plus DPV576 resulted in the reduction of the IC50 to 1/4th.This was associated with increased incidences of holes inside the cells as compared with control untreated cells.We conclude that DPV576 is an effective chemo-sensitizer as indicated by the reversal of HL60/AR cells to DNR and may represent a potential novel adjuvant for the treatment of chemo-resistant human myeloid leukemia.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.

ABSTRACT
Recently nanoparticles have been extensively studied and have proven to be a promising candidate for cancer treatment and diagnosis. In the current study, we examined the chemo-sensitizing activity of a mixture of nanodiamond (ND) and nanoplatinum (NP) solution known as DPV576, against multidrug-resistant (MDR) human myeloid leukemia (HL60/AR) and MDR-sensitive cells (HL60). Cancer cells were cultured with different concentrations of daunorubicin (DNR) (1 × 10 (-9)-1 × 10 (-6) M) in the presence of selected concentrations of DPV576 (2.5%-10% v/v). Cancer cell survival was determined by MTT assay, drug accumulation by flow cytometry and confocal laser scanning microscopy (CLSM), and holes and structural changes by atomic force microscopy (AFM). Co-treatment of HL60/AR cells with DNR plus DPV576 resulted in the reduction of the IC50 to 1/4th. This was associated with increased incidences of holes inside the cells as compared with control untreated cells. On the other hand, HL60 cells did not show changes in their drug accumulation post-treatment with DPV576 and DNR. We conclude that DPV576 is an effective chemo-sensitizer as indicated by the reversal of HL60/AR cells to DNR and may represent a potential novel adjuvant for the treatment of chemo-resistant human myeloid leukemia.

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Effect of DPV576 on the reversal of DNR resistance in HL60/AR cells. Cancer cells (1 × 104 well −1) were seeded in 96-well plates with DNR (1 × 10−9 to 1 × 10−6 M) and cultured in the presence or absence of various concentrations of DPV576 (2.5, 5, and 10% v/v) for 3 days. Cell survival was determined by MTT assay. Data represents the mean ± SD from three individual experiments, each in triplicate. The IC50 of DNR with DPV576 required 1/4th the amount of DNR as compared to the IC50 of DNR alone.Abbreviations: DNR, daunorubicin; MTT, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide; IC50, 50% inhibitory concentration.
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f1-ijn-8-2567: Effect of DPV576 on the reversal of DNR resistance in HL60/AR cells. Cancer cells (1 × 104 well −1) were seeded in 96-well plates with DNR (1 × 10−9 to 1 × 10−6 M) and cultured in the presence or absence of various concentrations of DPV576 (2.5, 5, and 10% v/v) for 3 days. Cell survival was determined by MTT assay. Data represents the mean ± SD from three individual experiments, each in triplicate. The IC50 of DNR with DPV576 required 1/4th the amount of DNR as compared to the IC50 of DNR alone.Abbreviations: DNR, daunorubicin; MTT, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide; IC50, 50% inhibitory concentration.

Mentions: HL60/AR cells were cultured with DNR at different concentrations (1 × 10 −9−1 × 10−6 M) in the presence or absence of DPV576 for 3 days. Cell survival and IC50 values were then determined by MTT assay. Figure 1 shows that DNR, as expected, inhibited the survival of cancer cells in a dose-dependent manner and that the IC50 of DNR alone was 3.1 μM. However, when the cells were co-cultured with DPV576 plus DNR, we noticed a decrease in cell survival that was also dose dependent of DPV576 and maximized at 10% v/v. Subsequently, the IC50 was significantly reduced, reaching 0.8 μM at 10% v/v.


Nano-hole induction by nanodiamond and nanoplatinum liquid, DPV576, reverses multidrug resistance in human myeloid leukemia (HL60/AR).

Ghoneum A, Sharma S, Gimzewski J - Int J Nanomedicine (2013)

Effect of DPV576 on the reversal of DNR resistance in HL60/AR cells. Cancer cells (1 × 104 well −1) were seeded in 96-well plates with DNR (1 × 10−9 to 1 × 10−6 M) and cultured in the presence or absence of various concentrations of DPV576 (2.5, 5, and 10% v/v) for 3 days. Cell survival was determined by MTT assay. Data represents the mean ± SD from three individual experiments, each in triplicate. The IC50 of DNR with DPV576 required 1/4th the amount of DNR as compared to the IC50 of DNR alone.Abbreviations: DNR, daunorubicin; MTT, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide; IC50, 50% inhibitory concentration.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3722034&req=5

f1-ijn-8-2567: Effect of DPV576 on the reversal of DNR resistance in HL60/AR cells. Cancer cells (1 × 104 well −1) were seeded in 96-well plates with DNR (1 × 10−9 to 1 × 10−6 M) and cultured in the presence or absence of various concentrations of DPV576 (2.5, 5, and 10% v/v) for 3 days. Cell survival was determined by MTT assay. Data represents the mean ± SD from three individual experiments, each in triplicate. The IC50 of DNR with DPV576 required 1/4th the amount of DNR as compared to the IC50 of DNR alone.Abbreviations: DNR, daunorubicin; MTT, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide; IC50, 50% inhibitory concentration.
Mentions: HL60/AR cells were cultured with DNR at different concentrations (1 × 10 −9−1 × 10−6 M) in the presence or absence of DPV576 for 3 days. Cell survival and IC50 values were then determined by MTT assay. Figure 1 shows that DNR, as expected, inhibited the survival of cancer cells in a dose-dependent manner and that the IC50 of DNR alone was 3.1 μM. However, when the cells were co-cultured with DPV576 plus DNR, we noticed a decrease in cell survival that was also dose dependent of DPV576 and maximized at 10% v/v. Subsequently, the IC50 was significantly reduced, reaching 0.8 μM at 10% v/v.

Bottom Line: Co-treatment of HL60/AR cells with DNR plus DPV576 resulted in the reduction of the IC50 to 1/4th.This was associated with increased incidences of holes inside the cells as compared with control untreated cells.We conclude that DPV576 is an effective chemo-sensitizer as indicated by the reversal of HL60/AR cells to DNR and may represent a potential novel adjuvant for the treatment of chemo-resistant human myeloid leukemia.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.

ABSTRACT
Recently nanoparticles have been extensively studied and have proven to be a promising candidate for cancer treatment and diagnosis. In the current study, we examined the chemo-sensitizing activity of a mixture of nanodiamond (ND) and nanoplatinum (NP) solution known as DPV576, against multidrug-resistant (MDR) human myeloid leukemia (HL60/AR) and MDR-sensitive cells (HL60). Cancer cells were cultured with different concentrations of daunorubicin (DNR) (1 × 10 (-9)-1 × 10 (-6) M) in the presence of selected concentrations of DPV576 (2.5%-10% v/v). Cancer cell survival was determined by MTT assay, drug accumulation by flow cytometry and confocal laser scanning microscopy (CLSM), and holes and structural changes by atomic force microscopy (AFM). Co-treatment of HL60/AR cells with DNR plus DPV576 resulted in the reduction of the IC50 to 1/4th. This was associated with increased incidences of holes inside the cells as compared with control untreated cells. On the other hand, HL60 cells did not show changes in their drug accumulation post-treatment with DPV576 and DNR. We conclude that DPV576 is an effective chemo-sensitizer as indicated by the reversal of HL60/AR cells to DNR and may represent a potential novel adjuvant for the treatment of chemo-resistant human myeloid leukemia.

Show MeSH
Related in: MedlinePlus