Effect of Allium senescens Extract on Sorafenib Resistance in Hepatocarcinoma Cells
and Seunggwan Lee 1,*Round 1
Reviewer 1 Report
I read an interesting and comprehensive research work entitled ‘Attenuation of drug resistance using the Allium senescens extract and p-coumaric acid in hepatocarcinoma cells’. The concept of the manuscript completely fits and is suitable to publish in Applied Sciences. This manuscript is generally well written and clearly presented however still needs to address many comments and thus require major revision.
English and grammar mistakes are present. The author should check the manuscript by native English Speaker to improve the quality of the manuscript.
Title should be modified in a precise way. Provide a nice graphical abstract representing the overview of the MS with key highlights.
In the introduction section, write the novelty of the work and the problem statement clearly. Authors should discuss different treatment methods for Hepatocellular carcinoma.
The detailed discussion about the novelty, significance of your research work and research gap relative to the literature is essential.
Authors used many abbreviations however not mentioned their full form somewhere, For chemicals, instruments give all details.
How did they cultivate the HePG2 cell line? Allium senescens extract gives details of extract preparation. Table 2 is not essential and instead give all details in the text. Operational conditions of flow cytometry should be provided.
Is Allium senescens extract suitable to treat other cancers?
Write the practical applications and future research perspectives and challenges by adding a new section before conclusions.
What are the limitation to use this methodology for commercial application?
The conclusion of the study is not discussed with the specific output obtained from the study, it could be modified with precise outcomes with a take home message.
Author Response
I read an interesting and comprehensive research work entitled ‘Attenuation of drug resistance using the Allium senescens extract and p-coumaric acid in hepatocarcinoma cells’. The concept of the manuscript completely fits and is suitable to publish in Applied Sciences. This manuscript is generally well written and clearly presented however still needs to address many comments and thus require major revision.
English and grammar mistakes are present. The author should check the manuscript by native English Speaker to improve the quality of the manuscript.
Answer 1. We revised the manuscripts with English editing service.
Title should be modified in a precise way. Provide a nice graphical abstract representing the overview of the MS with key highlights.
Answer 2. We revised the title and presented graphical abstract
In the introduction section, write the novelty of the work and the problem statement clearly. Authors should discuss different treatment methods for Hepatocellular carcinoma. The detailed discussion about the novelty, significance of your research work and research gap relative to the literature is essential.
Answer 3. We described for the different methods, novelty and problem in introduction.
Authors used many abbreviations however not mentioned their full form somewhere, For chemicals, instruments give all details.
Answer 4. We add the full form in all abbreviations and described for the instruments
How did they cultivate the HePG2 cell line? Allium senescens extract gives details of extract preparation. Table 2 is not essential and instead give all details in the text. Operational conditions of flow cytometry should be provided.
Answer 7 Guide line from ministry of food and drug safety (MFDA) in Korea recommends HepG2 cell line for experiment with a hepatic functional material. We revised M&M accordantly with the comments.
Is Allium senescens extract suitable to treat other cancers?
Answer 8. In our projects, the extract affects to a cell model associated with parkinson’s disease and I think the extract is effective for reproductive cancers.
Write the practical applications and future research perspectives and challenges by adding a new section before conclusions.
Answer 9. We added the section before the conclusion.
What are the limitation to use this methodology for commercial application?
Answer 10. In our research, although there is low cytotoxicity of the extract in cell lines and strains, in vivo experiment is proposed to apply a bio-material for functional food. We have been studying for the extract inducing exosomes for synthesis functional liposomes containing microRNAs.
The conclusion of the study is not discussed with the specific output obtained from the study, it could be modified with precise outcomes with a take home message.
Answer 11. We discussed for specific output and outcomes of our research in the conclusion.
Reviewer 2 Report
The topic and results of the manuscript entitled "Attenuation of drug resistance by Allium senescens extract and p-coumaric acid in hepatocarcinoma cells" are interesting, but the presentation of the results should be significantly improved. In addition, I missed the results of some experiments that are necessary for this type of study. I propose the following amendments:
- Correction of English is necessary to make MS easier to understand.
- "p-coumaric acid" should be omitted from the title as only one experiment has been performed with it.
- Table 1 should be listed as supplementary material
- The information in Table 2 should be provided in the text only
- Non-standard units (1M = 1mol / L) are used in line 123,126. Please fix them.
- In the methods, please add information on the concentration of A.S. (CA) and exposure time used for all experiments
- Use a larger font of letters and numbers in all images to make them easier to read
- In Fig. 1 omit part B (information is clear from part A)
- Please, present the effect of A.S. (over a wide range of concentrations and several incubation times) on the viability of sensitive (S) and resistant (R) HepG2 cells.
- Please provide a comparison of mRNA and protein levels of all transporters studied in S and R HepG2 cells
- In the legends to Figure 4-6, complete the A.S. (CA) and exposure time
- In Fig. 5, only state the quantification of individual transporters and omit the records from the detector. Why were ABCB1 and ABCG2 not quantified? Please fill in these results.
- Please correct the legend in Fig. 5, there are some errors.
Author Response
The topic and results of the manuscript entitled "Attenuation of drug resistance by Allium senescens extract and p-coumaric acid in hepatocarcinoma cells" are interesting, but the presentation of the results should be significantly improved. In addition, I missed the results of some experiments that are necessary for this type of study. I propose the following amendments:
Correction of English is necessary to make MS easier to understand.
Answer 1. We revised our manuscript through English editing service.
"p-coumaric acid" should be omitted from the title as only one experiment has been performed with it.
Answer 2. We revised the title.
Table 1 should be listed as supplementary material
Answer 3. We changed the table1 as supplementary file S2
The information in Table 2 should be provided in the text only
Answer 4. We describe the table2 in M&M
Non-standard units (1M = 1mol / L) are used in line 123,126. Please fix them.
Answer 5. We revised the units
In the methods, please add information on the concentration of A.S. (CA) and exposure time used for all experiments
Answer 6. We added the concentration and exposure time.
Use a larger font of letters and numbers in all images to make them easier to read
Answer 7. We revised the all images
In Fig. 1 omit part B (information is clear from part A)
Answer 8. We revised the Figure 1
Please, present the effect of A.S. (over a wide range of concentrations and several incubation times) on the viability of sensitive (S) and resistant (R) HepG2 cells.
Answer 9. We added supplementary data (S3) for the comment.
Please provide a comparison of mRNA and protein levels of all transporters studied in S and R HepG2 cells
Answer 10. With double checking of our raw data, the mRNA and protein levels were displayed in fig 4 and fig 5.
In the legends to Figure 4-6, complete the A.S. (CA) and exposure time
Answer 11. We added the exposure times in M&M.
In Fig. 5, only state the quantification of individual transporters and omit the records from the detector. Why were ABCB1 and ABCG2 not quantified? Please fill in these results.
Answer 12. With additional experiments and double checking of raw data, we revised the fig5 and manuscript.
Please correct the legend in Fig. 5, there are some errors.
Answer 13. We revised the legend in Fig. 5
Round 2
Reviewer 1 Report
My recommendation is
The authors have substantially revised the manuscript according to the comments.
The present form of the manuscript can be accepted for publication.
Thanks and regards
Author Response
I appreciate for your comments.
Reviewer 2 Report
Certain improvements are still needed:
-In the legends to Figure 4-6, please, complete the A.S. (CA) concentration and exposure time
-Check the correctness of the units for the concentrations used. Micromol per microliter = millimolar concentration. This is an incredibly high concentration, the usual concentration is an order of magnitude lower (micromolar i.e. micromol per liter)
-In Fig. 5, only state the quantification of individual transporters and omit the records from the detector.
Author Response
-In the legends to Figure 4-6, please, complete the A.S. (CA) concentration and exposure time
Answer: We already described the exposure time at line 81
-Check the correctness of the units for the concentrations used. Micromol per microliter = millimolar concentration. This is an incredibly high concentration, the usual concentration is an order of magnitude lower (micromolar i.e. micromol per liter)
Answer: We checked and revised all units in manuscript.
-In Fig. 5, only state the quantification of individual transporters and omit the records from the detector.
Answer: We attached table S2 (the records from the detector) in supplementary data
