Antimetastatic Activity of Apoptolidin A by Upregulation of N-Myc Downstream-Regulated Gene 1 Expression in Human Colorectal Cancer Cells
, Jiyoon Park, Seung Ho Oh, Ji Yun Lee, Eun Seo Bae, Hyen Joo Park, Dong-Chan Oh and Sang Kook Lee *Round 1
Reviewer 1 Report
The authors in the manuscript characterize the effect of cyclic lactone apoptolidin on colorectal cell lines. They show a dose dependent growth inhibition of apoptolidin in three CRC cell lines, cell cycle arrest, migration, intrinsic apoptosis. Furthermore, they demonstrate that NDRG1 expression is restored following incubation with apoptolidin. They further link the downregulation of NDRG1 by sirna leads to anti metastatic activity following apoptolidin exposure. Although restoration of NDRG1 is a desired feature, the mechanism around is vague. Authors should convince the reader on the specificity of NDRG1 in the treatment outcome. The readability is good and images are neat and good resolution.
Following issues need to be addressed before the manuscript is considered for publication.
Major Points
- Authors do not describe how did they calculate the IC50
- Cell proliferation assay and IC50 in a non-tumor cell line is required in Fig1
- Authors should discuss the mechanism of NDRG1 elevation following apoptolidin exposure. Have they checked levels of other TSGs, eg. P53 etc
Minor Points
- The WB images should be marked with their respective molecular weight in the figures
Author Response
Please see the attachment.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
The article is relevant research about investigation drug candidates that inhibit Colorectal cancer metastasis.
The article demonstrate, that these findings suggest that apoptolidin A exerts antiproliferative and antimetastatic activities by regulating the NDRG1-activated EMT pathway in CRC cells.
The English language and style should be checked. In the conclusions, the importance of this study should be emphasized more.
The statistical value t and p should be in Italic (in all article).
The article is accepted to publication.
Author Response
Please see the attachment.
Author Response File: Author Response.pdf
Round 2
Reviewer 1 Report
The Authors have addressed the comments appropriately.
Manuscript is recommended for publication.
