Therapeutic Effects of Synthetic Triblock Amphiphilic Short Antimicrobial Peptides on Human Lung Adenocarcinoma

Round 1

Reviewer 1 Report

In this manuscript, the authors describe the biological evaluation of triblock antimicrobial peptides as anticancer therapeutics. Structure-activity relationship on a series of peptides was studied in vitro and in vivo. It was found that K4F6K4 showed good potency against cancers cell but less cytotoxicity against normal cell. Overall the study was well performed and will be of interest to the scientific community. The reviewer only have a few minor comments.

1. Antimicrobial activities of these peptides have already described in previous studies so the word "original" in the title is misleading.
2. The whole study was performed on human lung adenocarcinoma A549 and normal human lung fibroblast cells. It will be interesting to study the anticancer activity and selectivity with additional cancer and normal cell lines.
3. There are too many speculations in the proposed mechanism. It will be good if the authors can demonstrate that specific interaction is caused by the binding to more negatively charged tumor cells. If the binding is mediated by heparin sulfates, the addition of heparin sulfates to the assay may competitively inhibit the antitumor activity of the peptide.   

Author Response

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Author Response File: Author Response.docx

Reviewer 2 Report

In this contribution, He and coworkers evaluated the therapeutic effects of short amphiphilic antimicrobial peptides on human lung adenocarcinoma. The authors carried out a systematic study to assess the anticancer activity of the different synthetic peptides. They took advantage of diverse experimental techniques generating a considerable set of data. Figures and Tables are well-presented, even if sometimes comments on results could be improved (e.g., lines 201-205, 211-221).

Prior to formal acceptance the following points should be fixed:

-              English language style should be revised, in particular in Abstract and Introduction.

-              For cell viability assays, cells were treated with increasing concentrations of peptide for long times (up to 48h), any tests on the peptide resistance to proteolytic degradation in cellular medium were conducted?

-              In the Discussion, authors stated “Although the mechanisms of AMPs exhibiting anticancer activity have not yet been studied thoroughly, it’s sure that structures determine functions”, to corroborate this statement, at least a preliminary evaluation on conformation of the selected peptides in membrane mimicking environment should be presented.

 

Minor points:

-              Throughout text “in vitro” and “in vivo” should be written in italics.

-              Introduction: the sentence “Although conventional treatment is mainly surgery combined with chemotherapy and radiotherapy.” is nonsense.

-              p. 1, line 22: “analogues” not “analogous”.

-              p. 4, line 179: “corresponding” not “corresponded”.

Author Response

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Author Response File: Author Response.pdf

Reviewer 3 Report

The manuscript presented is a consolidation of the results for a study of a panel of synthetic antimicrobial peptides on a tumor model in vitro and in vivo systems. It must be noted that the problem of searching for new low-toxic natural compounds with antitumor properties does not lose its relevance. In this regard, the available data on a high level of AMP activity on tumors is an extremely unique event that requires detailing at the cellular and molecular levels. The scientific level of this article is assessed as quite high; there is a number of comments on the text:

1. The selected range of effective concentrations (62.5-1000 µg/ml) is quite high. What was the reason for such a choice?
2. There is no information in the work about the primary structures of peptides, their molecular weights, and basic physico-chemical properties. It looks more like an abstraction.
3. Have the efficacy of the selected AMPs been studied on other tumor cell lines? At least, in vitro models? They are needed to be compared.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

Manuscript can be accepted in this revised version