Anti-Leukemic Effects of Idesia polycarpa Maxim Branch on Human B-Cell Acute Lymphoblastic Leukemia Cells
Round 1
Reviewer 1 Report
The manuscript "Anti-leukemic effects of Idesia polycarpa Maxim. branch in human B-cell acute lymphoblastic leukemia cells" shows a study of a trial of 100 plant extracts against human B-cell acute lymphoblastic leukemia cells. The objectives are clear, but the authors claim the effect of plant extract from Idesia polycarpa Maxim is a promising therapeutic in human leukemia.
Despite the interest in exploring natural compounds against human leukemia, the study has serious flaws in statistical analysis. The section results shown in Table 1 have no unit of values and do not indicate the error of measurements. Also, they did not compare the BM values with-CCRF-SB values in a way to show that the data differ or not differ. In an awkward way, the authors show the "Differential toxicity" when they must show the therapeutic index or selective index between the two line cells.
The authors must improve the statistical analysis and resubmit the manuscript.
Author Response
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Author Response File: 
Author Response.docx
Reviewer 2 Report
Dear Authors
Thank you for giving me the chance to look at your work, which was quiet interesting. I have some comments and small corrections.
· In the selection of the plants add that they are traditionally used from the whole flora how many families.
· The plant Idesia you add more information in the introduction about the plant uses in traditional medicine and a short description.
· What is meant by branches is it stem botanically.
· Plant material: added voucher specimen
· In the discussion write the constituents of the plant , which might be responsible for the effect
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Comment |
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Abstract |
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15 |
From South Korean Flora |
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17 |
In this screening |
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56 |
Omit This study change to previous report |
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60 |
improve |
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72 |
Used in traditional medicine |
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73 |
Common name |
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88 |
Chemicals used |
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93 |
Western |
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140 |
Sigma add City and Country |
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183 |
These diterpenes |
Author Response
Please see the attachment
Author Response File: Author Response.docx
Reviewer 3 Report
The authors in their study evaluate the antiproliferative effects of Idesia polycarpa Maxim. branch (IMB) toward a leukemic cell line, CCRF-SB. This plant extract inhibited the proliferation of CCRF-SB cells and induced apoptosis through the intrinsic pathway. IMB increased the expression of PAX5 and IKZF1, key regulatory genes for ALL cell differentiation. Furthermore, IMB increased the sensitivity of cells to a glucocorticoid, increased glucocorticoid receptor alpha expression, and down-regulated mTOR and MAPK signaling pathways involved in glucocorticoid resistance.
I have the following questions for the authors:
The authors mention that cell viability analysis was determined toward CCRF-SB and normal mouse bone marrow cells at different cell densities. CCRF-SB cells were plated at a density of 4 × 104 cells and normal bone marrow cells at 5 × 105 cells per well. The higher cell density would render normal cells less sensitive to the examined extract. Could the authors clarify the purpose of this seeding, and was a similar cell density for the cell lines taken into consideration?
The authors mention that IMB displays lower cytotoxicity toward normal BM cells than CCRF-SB cells. The relative cell viability of CCRF-SB cells (Figure 1A) and BM cells (Figure 1B) should be compared (presented on the same graph), and the statistical significance should be analyzed.
In Table 1, the values presented in the columns under the presented cell lines should be clarified. Do these values represent IC50 values?
The colony-forming assay should be additionally analyzed quantitatively.
The images in Figure 3C are illegible. A higher magnification of the images could be presented along with a scale bar on the images.
Densitometric analysis of western blots shown in Figure 5C should be performed This would more clearly demonstrate the downregulation of some of the presented proteins.
Since the authors performed in vivo analysis of the toxicity of IMB, why weren’t the anti-leukemic effects of this extract examined in vivo alongside toxicity analysis?
Author Response
Please see the attachment
Author Response File: Author Response.docx
Round 2
Reviewer 1 Report
The authors addressed all issues well, improving the quality of the manuscript.
Reviewer 3 Report
The authors have addressed my comments and modified their manuscript according to the suggestions. Thus, I find this manuscript appropriate for publication.
