Comparative Study of the Anticancer Effects of Selenium Nanoparticles and Selenium Nanorods: Regulation of Ca²⁺ Signaling, ER Stress and Apoptosis

Round 1

Reviewer 1 Report

This is an interesting study looking at the effect of either selenium nanoparticles or selenium nanorods on the human glioblastoma cancer cell line A-172 in comparison to a mouse fibroblast cell line L-929. The authors determined that selenium nanorods were more effective at inducing apoptosis then selenium nanoparticles without inducing necrosis in A-172 cells. The authors suggest this is due to calcium rise in which correlates with increased pro-apoptotic genes in the A-172 cells but not the L-929 cells. While interesting, I believe the study could be improved by a direct comparison between a human cancer cell line and a human fibroblast cell line rather than a mouse. 

Specific Comments:

1. Need to include author contributions, IRB approval and funding sources. All three are missing.

2. Figures 4 and 5 - It would be helpful to have a bold label indicating which cell line was used for each figure. Otherwise, it is a little confusing as presented as to which cell line is being used to assess the impact of the SeNrs and SeNPs on apoptosis and necrosis in these cell lines. 

3. A-172 is a human glioblastoma cell line while L-929 is a mouse fibroblast cell line. Why not use a human fibroblast cell line to compare the impact of the SeNPs and SeNrs? Differences in results between the two cell lines could be simply due to the use of two different species.  

Some minor grammatical errors, otherwise quality of English language is generally good. 

Author Response

Reviewer #1

Comments 1.1

Need to include author contributions, IRB approval and funding sources. All three are missing.

Reply 1.1

We thank the reviewer for taking the time to read our manuscript and for his valuable comments. We have added author contributions, IRB approval and funding sources to the text of the manuscript.

Comments 1.2

Figures 4 and 5 - It would be helpful to have a bold label indicating which cell line was used for each figure. Otherwise, it is a little confusing as presented as to which cell line is being used to assess the impact of the SeNrs and SeNPs on apoptosis and necrosis in these cell lines. 

Reply 1.2

We agree. Thank you. Added

Comments 1.3

A-172 is a human glioblastoma cell line while L-929 is a mouse fibroblast cell line. Why not use a human fibroblast cell line to compare the impact of the SeNPs and SeNrs? Differences in results between the two cell lines could be simply due to the use of two different species.  

Reply 1.3

We agree with the opinion of the respected reviewer. The objective of this work was to compare the effects of two types of nanoparticles on cancer and “healthy” cells. Of course, it would be more correct if we used human fibroblasts, but it is extremely difficult for us to obtain such a cell line in the foreseeable future. One might suggest using the human HEK-293 cell line, which is used in a number of studies, as a control. However, there is growing evidence that these cells cannot be characterized as “healthy”. These cells are characterized as a non-cancerous, but oncogenic cell line. In view of the similarity of most physiological and pathophysiological processes in humans and mice, a comparative analysis of the effects of nanoparticles relative to a mouse cell line can be considered acceptable.

Reviewer 2 Report

The manuscript entitled “Comparative study of the anticancer effects of selenium nanoparticles and selenium Nanorods. Regulation of Ca2+ signaling, ER stress and apoptosis” deals with the therapeutic potential of selenium nanoparticles an nanorods. The therapeutic usage of nanomaterials is a hot topic in cancer research, falls within the scope of the journal and would be interesting for the general readership.

The manuscript is well structured, and the applied methodology is adequate and the main results are clearly presented. Apart from language editing, some minor changes are required:

-       Please rephrase the sentence in lines 45 and 46, since the meaning is greatly affected by the grammar and syntax errors.

-       Please use g force beside rpm for centrifuge speed in line 107, since it is more informative.

-       More details about the PCR procedure are required (e.g. primer sequences), since the cited article does not contain all the relevant data.

-       The first sentence of the Conclusions section can be deleted, since it is more related to the applied methodology, instead of pointing out the main results from comparing the anticancer activities of two types of nanoparticles.

Minor-to-moderate English editing is required, since some of the parts of the manuscript are difficult to understand, or have the meaning which is opposite  to the intended.

Author Response

Reviewer #2

Comment 2.1

Please rephrase the sentence in lines 45 and 46, since the meaning is greatly affected by the grammar and syntax errors.

Reply 2.1

We thank the reviewer for taking the time to read our manuscript and for his valuable comments. Thank you. Paraphrased. (However, these methods have a number of side effects - toxic effects on healthy organs and tissues).

Comment 2.2

Please use g force beside rpm for centrifuge speed in line 107, since it is more informative.

Reply 2.2

Added (4200 rpm, rotor radius 0.12 m, Relative Centrifugal Force ~2400 g).

Comment 2.3

More details about the PCR procedure are required (e.g. primer sequences), since the cited article does not contain all the relevant data.

Reply 2.3

Primer sequences added (Table 1, 2)

Comment 2.4

The first sentence of the Conclusions section can be deleted, since it is more related to the applied methodology, instead of pointing out the main results from comparing the anticancer activities of two types of nanoparticles.

Reply 2.4

Deleted