| Title |
Curcumin enhances the cytogenotoxic effect of etoposide in leukemia cells through induction of reactive oxygen species
|
|---|---|
| Published in |
Drug Design, Development and Therapy, February 2016
|
| DOI | 10.2147/dddt.s92687 |
| Pubmed ID | |
| Authors |
Monika A Papież, Wirginia Krzyściak, Krzysztof Szade, Karolina Bukowska-Straková, Magdalena Kozakowska, Karolina Hajduk, Beata Bystrowska, Jozef Dulak, Alicja Jozkowicz |
| Abstract |
Curcumin may exert a more selective cytotoxic effect in tumor cells with elevated levels of free radicals. Here, we investigated whether curcumin can modulate etoposide action in myeloid leukemia cells and in normal cells of hematopoietic origin. HL-60 cell line, normal myeloid progenitor cluster of differentiation (CD)-34(+) cells, and granulocytes were incubated for 4 or 24 hours at different concentrations of curcumin and/or etoposide. Brown Norway rats with acute myeloid leukemia (BNML) were used to prove the influence of curcumin on etoposide action in vivo. Rats were treated with curcumin for 23 days and etoposide was administered for the final 3 days of the experiment. Curcumin synergistically potentiated the cytotoxic effect of etoposide, and it intensified apoptosis and phosphorylation of the histone H2AX induced by this cytostatic drug in leukemic HL-60 cells. In contrast, curcumin did not significantly modify etoposide-induced cytotoxicity and H2AX phosphorylation in normal CD34(+) cells and granulocytes. Curcumin modified the cytotoxic action of etoposide in HL-60 cells through intensification of free radical production because preincubation with N-acetyl-l-cysteine (NAC) significantly reduced the cytotoxic effect of curcumin itself and a combination of two compounds. In contrast, NAC did not decrease the cytotoxic effect of etoposide. Thus, oxidative stress plays a greater role in the cytotoxic effect of curcumin than that of etoposide in HL-60 cells. In vitro results were confirmed in a BNML model. Pretreatment with curcumin enhanced the antileukemic activity of etoposide in BNML rats (1.57-fold tumor reduction versus etoposide alone; P<0.05) and induced apoptosis of BNML cells more efficiently than etoposide alone (1.54-fold change versus etoposide alone; P<0.05), but this treatment protected nonleukemic B-cells from apoptosis. Thus, curcumin can increase the antileukemic effect of etoposide through reactive oxygen species in sensitive myeloid leukemia cells, and it is harmless to normal human cells. |
Mendeley readers
The data shown below were compiled from readership statistics for 42 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 42 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 6 | 14% |
| Student > Master | 4 | 10% |
| Professor > Associate Professor | 3 | 7% |
| Student > Doctoral Student | 3 | 7% |
| Student > Bachelor | 2 | 5% |
| Other | 9 | 21% |
| Unknown | 15 | 36% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 6 | 14% |
| Medicine and Dentistry | 5 | 12% |
| Pharmacology, Toxicology and Pharmaceutical Science | 5 | 12% |
| Agricultural and Biological Sciences | 4 | 10% |
| Environmental Science | 1 | 2% |
| Other | 5 | 12% |
| Unknown | 16 | 38% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 05 February 2016.
All research outputs
#22,935,114
of 25,576,275 outputs
Outputs from Drug Design, Development and Therapy
#1,760
of 2,274 outputs
Outputs of similar age
#349,004
of 407,504 outputs
Outputs of similar age from Drug Design, Development and Therapy
#74
of 90 outputs
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We're also able to compare this research output to 90 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.