This research article shows that specific doses of the dietary flavonoid quercetin reduce hydrogen peroxide-induced apoptosis in K562 leukemia cells. Because reactive oxygen species are involved in the cytotoxic activity of some forms of cancer therapy (radiotherapy, some anticancer drugs), the authors conclude that uncontrolled consumption of antioxidants such as quercetin may reduce the efficacy of these forms of therapy and, therefore, should be strictly controlled.

I completely agree with the conclusion of this article. My main criticism is on the originality of the topic, as similar findings have been reported previously in the literature. The antioxidant capacity of the dietary flavonoid quercetin is already well known. As mentioned by the authors, the ability of quercetin to prevent apoptosis induction by hydrogen peroxide has already been reported (reference 22). The possible interference of dietary antioxidants with chemotherapy has already been reported and discussed elsewhere (http://www.ncbi.nlm.nih.gov/pubmed/16166076 ).

The authors observe that quercetin prevents hydrogen peroxide-induced apoptosis in K562 leukemia at a non-toxic concentration of 100 microM. We have observed that such concentration of quercetin is highly cytotoxic in K562; perhaps this apparent discrepancy is due to the different conditions used in our experiments (XTT assay, 5-days exposure: http://www.ncbi.nlm.nih.gov/pubmed/20025993 ).

The low oral bioaviability of quercetin should have been considered when discussing the results. Such low bioavailability means that a 100 microM concentration of quercentin cannot be reached in plasma and tissues (other than those of the gastrointestinal tract) after oral ingestion. However, in vivo evidence indicates that the low concentrations of quercetin achievable in plasma and tissues after oral ingestion can induce antioxidant effects and, therefore, reduce the efficacy of some forms of cancer therapy.

I share the criticisms raised by Prof. Melek Ozturk and Dr. John G Edwards in their reviews, which should be dealt with in a possible revised version of the article.

Cancer research, flavonoids

There are afew  errors or missing words in the manuscript.

METHOD: Annexin V staining assay: After induction with H2O2 ………… suspended in 1x? binding buffer

Annexin V-FITC (what is it source or company) method must be explained or a reference must be adressed

RESULTS: …..For the time-course …………,400 and 500 mM of quercetin for 3 ????

The expressed stastical analysis values  must be explaines (mean ± SD??). It should write in the methods or under the figures.

For the statistical comparison of the three groups it can be used ANOVA test

In the Figure 1-2 . P value dots are not understandable. Dots must be redesigned on the suitable ranges.

In the Figure 3: Protective effect ………by Annexin V/PI flow cytometry assay. * P<0.05, ** P<0.01, ***P<0.001 there is no indication on the bars for the ***value

REFERENCES: 14. Jung JH, Lee JO, Kim Je completeH, Lee SK, You GY, Park SH, et al. Quercetin suppresses HeLa cell viability via AMPK-induced HSP70 and EGFR down-regulation. J Cell Physiol.  DATE? May;223(2):408-14.

Apoptosis

The use of herbals as remedies for aliments has been empirically driven. And science has followed on to validate their use.  Such is the focus of the present paper, to examine the potential use of quercetin as an antioxidant. The authors find that in moderate does quercetin does offer some protection from the oxidants stress hydrogen peroxide.  However, there are some things left undone that would clarify the authors observations.

Some parts of the paper are difficult to read; editing for English lanuage would help.

Methods; What were the concentrations of AnnexinV-FITC and propidium iodide used for the flow cytometry analysis?

Figures 1-3; Are the error bars shown standard deviation or standard error of the mean?  What are the samples sizes

Since the authors used flow cytometry it would have been nice to have seen a quadrant dotplot illustrating the shifts in the cell counts from viable to early apoptotic to dead cells.

In Figure 3 there are 3 groups and an ANOVA test should have been used to make the statistical comparisons followed by a post-hoc test.

mitochondrial dysfunction