Title: Amarogentin suppresses cell proliferation and EMT process through inducing ferroptosis
in colorectal cancer
Version: 2 Date: 19 Dec 2024
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-"Colorectal cancer (CRC) is one swart tumor in human" – The term "swart" is unclear and
should likely be replaced with "serious" or "common."
-"The characteristics of CRC contain strong concealment" – This phrasing is awkward; it should
be reworded as "CRC is characterized by its ability to remain asymptomatic" or similar.
-While the manuscript suggests that AG induces ferroptosis in CRC cells, it lacks a detailed
mechanistic explanation. The molecular pathways or specific interactions through which AG
modulates ferroptosis (e.g., the involvement of key ferroptosis regulators like GPX4, ACSL4,
or FSP1) are not sufficiently discussed.
-The authors mention the suppression of Nrf2/HO-1/GPX4 activation by AG, but further
explanation of how AG interferes with these pathways is needed. For example, does AG directly
affect gene expression, protein stability, or post-translational modifications of these key players?
-The in vivo study is not described in sufficient detail. While the tumor volume and weight
reduction are mentioned, the specific data (e.g., percentage of tumor growth inhibition, statistical
significance) should be presented to better demonstrate AG’s efficacy in vivo.
-While the Nrf2/HO-1/GPX4 axis is mentioned, there is still limited discussion on how AG
specifically affects these pathways. For example, how does AG modulate Nrf2 activation? Is
AG directly influencing the transcriptional activity of Nrf2, or is it altering upstream signaling
events? It would be helpful to provide a more detailed mechanistic explanation or suggest
potential experiments to elucidate these aspects further.
-While the PTC model is mentioned, the discussion does not delve into how AG might interact
with various components of the tumor microenvironment (e.g., immune cells, stromal cells) that
are present in the PTC model. Exploring whether AG also affects immune cells or fibroblasts
in the tumor microenvironment could provide a more comprehensive understanding of its
therapeutic potential.
Title: Amarogentin suppresses cell proliferation and EMT process through inducing ferroptosis
in colorectal cancer
Version: 2 Date: 19 Dec 2024
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-"Colorectal cancer (CRC) is one swart tumor in human" – The term "swart" is unclear and
should likely be replaced with "serious" or "common."
-"The characteristics of CRC contain strong concealment" – This phrasing is awkward; it should
be reworded as "CRC is characterized by its ability to remain asymptomatic" or similar.
-While the manuscript suggests that AG induces ferroptosis in CRC cells, it lacks a detailed
mechanistic explanation. The molecular pathways or specific interactions through which AG
modulates ferroptosis (e.g., the involvement of key ferroptosis regulators like GPX4, ACSL4,
or FSP1) are not sufficiently discussed.
-The authors mention the suppression of Nrf2/HO-1/GPX4 activation by AG, but further
explanation of how AG interferes with these pathways is needed. For example, does AG directly
affect gene expression, protein stability, or post-translational modifications of these key players?
-The in vivo study is not described in sufficient detail. While the tumor volume and weight
reduction are mentioned, the specific data (e.g., percentage of tumor growth inhibition, statistical
significance) should be presented to better demonstrate AG’s efficacy in vivo.
-While the Nrf2/HO-1/GPX4 axis is mentioned, there is still limited discussion on how AG
specifically affects these pathways. For example, how does AG modulate Nrf2 activation? Is
AG directly influencing the transcriptional activity of Nrf2, or is it altering upstream signaling
events? It would be helpful to provide a more detailed mechanistic explanation or suggest
potential experiments to elucidate these aspects further.
-While the PTC model is mentioned, the discussion does not delve into how AG might interact
with various components of the tumor microenvironment (e.g., immune cells, stromal cells) that
are present in the PTC model. Exploring whether AG also affects immune cells or fibroblasts
in the tumor microenvironment could provide a more comprehensive understanding of its
therapeutic potential.
Please review this paper.
user
Title: Amarogentin suppresses cell proliferation and EMT process through inducing ferroptosis
in colorectal cancer
Version: 2 Date: 19 Dec 2024
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-"Colorectal cancer (CRC) is one swart tumor in human" – The term "swart" is unclear and
should likely be replaced with "serious" or "common."
-"The characteristics of CRC contain strong concealment" – This phrasing is awkward; it should
be reworded as "CRC is characterized by its ability to remain asymptomatic" or similar.
-While the manuscript suggests that AG induces ferroptosis in CRC cells, it lacks a detailed
mechanistic explanation. The molecular pathways or specific interactions through which AG
modulates ferroptosis (e.g., the involvement of key ferroptosis regulators like GPX4, ACSL4,
or FSP1) are not sufficiently discussed.
-The authors mention the suppression of Nrf2/HO-1/GPX4 activation by AG, but further
explanation of how AG interferes with these pathways is needed. For example, does AG directly
affect gene expression, protein stability, or post-translational modifications of these key players?
-The in vivo study is not described in sufficient detail. While the tumor volume and weight
reduction are mentioned, the specific data (e.g., percentage of tumor growth inhibition, statistical
significance) should be presented to better demonstrate AG’s efficacy in vivo.
-While the Nrf2/HO-1/GPX4 axis is mentioned, there is still limited discussion on how AG
specifically affects these pathways. For example, how does AG modulate Nrf2 activation? Is
AG directly influencing the transcriptional activity of Nrf2, or is it altering upstream signaling
events? It would be helpful to provide a more detailed mechanistic explanation or suggest
potential experiments to elucidate these aspects further.
-While the PTC model is mentioned, the discussion does not delve into how AG might interact
with various components of the tumor microenvironment (e.g., immune cells, stromal cells) that
are present in the PTC model. Exploring whether AG also affects immune cells or fibroblasts
in the tumor microenvironment could provide a more comprehensive understanding of its
therapeutic potential.
assistant