-->PONE-D-25-37431-->-->Classification and cytotoxic activity of Vietnamese Ganoderma ellipsoideum against human breast cancer MCF-7 cell lines-->-->PLOS ONE

Dear Dr. Tran,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Sep 23 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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We look forward to receiving your revised manuscript.

Kind regards,

Muhammad Zeeshan Bhatti, Ph.D

Academic Editor

PLOS ONE

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When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

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2. We noticed you have some minor occurrence of overlapping text with the following previous publication(s), which needs to be addressed:

https://www.researchsquare.com/article/rs-2421198/v1

https://www.tjnpr.org/index.php/home/article/view/5237

In your revision ensure you cite all your sources (including your own works), and quote or rephrase any duplicated text outside the methods section. Further consideration is dependent on these concerns being addressed.

3. Thank you for stating the following financial disclosure:

“Scholarship Program of the Vingroup Innovation Foundation (VINIF), Vingroup Big Data Institute (VINBIGDATA) (grant number: code VINIF.2020.TS.68).”

Please state what role the funders took in the study.  If the funders had no role, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."

If this statement is not correct you must amend it as needed.

Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf.

4. Please provide a complete Data Availability Statement in the submission form, ensuring you include all necessary access information or a reason for why you are unable to make your data freely accessible. If your research concerns only data provided within your submission, please write "All data are in the manuscript and/or supporting information files" as your Data Availability Statement.

5. Thank you for stating the following in the Acknowledgments Section of your manuscript:

“Trang Thi Thu Nguyen was funded by the Vingroup Joint Stock Company and supported by the PhD Scholarship Program of the Vingroup Innovation Foundation (VINIF), Vingroup Big Data Institute (VINBIGDATA) (grant number: code VINIF.2020.TS.68).”

We note that you have provided additional information within the Acknowledgements Section that is not currently declared in your Funding Statement. Please note that funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form.

Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows:

“Scholarship Program of the Vingroup Innovation Foundation (VINIF), Vingroup Big Data Institute (VINBIGDATA) (grant number: code VINIF.2020.TS.68).”

Please include your amended statements within your cover letter; we will change the online submission form on your behalf.

6. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. 

Additional Editor Comments (if provided):

Thank you for submitting your manuscript, "Classification and cytotoxic activity of Vietnamese Ganoderma ellipsoideum against human breast cancer MCF-7 cell lines," to PLOS ONE. The paper has been peer-reviewed and requires a major revision before it can be considered for publication.

Below is a summary of the required revisions:

1. It has been noted that the manuscript's primary focus is on the identification and characterization of Ganoderma ellipsoideum using in silico methods, with very little experimental work on cytotoxicity. Please revise the title to better reflect the core hypothesis and content of your research.
2. Please include a detailed description of the sample preparation and extraction methods in the section of Materials and Methods
3. To validate you’re in silico results, please perform a Western blotting experiment for protein identification
4. Cytotoxicity experiment results in the Tables 3 and 4 into a single table for clarity.
5. The resolution of Figures 3, 4, 5, and 6 is too low. Please submit high-resolution versions of these images.
6. The manuscript requires an extensive revision for grammar, syntax, and overall clarity. Please consider having it proofread by a native English speaker or a professional editing service.

We look forward to receiving your revised manuscript. Please ensure all comments are addressed in your resubmission.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

-->Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. -->

Reviewer #1: Yes

Reviewer #2: Partly

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-->2. Has the statistical analysis been performed appropriately and rigorously? -->

Reviewer #1: Yes

Reviewer #2: Yes

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-->3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.-->

Reviewer #1: Yes

Reviewer #2: Yes

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-->4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.-->

Reviewer #1: Yes

Reviewer #2: Yes

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-->5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)-->

Reviewer #1: Overall, this is a solid and well-structured study. The authors present their methodology clearly and acknowledge key limitations—such as the use of a single breast cancer cell line, the need for experimental validation of docking results, and the lack of compound isolation—which demonstrates good scientific transparency. The conclusions are adequately supported, and the paper aligns with the scope and standards of PLOS ONE. Only a few minor editorial corrections are needed before publication. Minor edits for clarity and consistency:

• There's a small typo in the phrase “Maximum Likehood” — it should be corrected to “Maximum Likelihood.”

• In the Results section, it would be helpful to write out “Maximum Likelihood (ML)” the first time it's mentioned, even though it's already explained in the Methods.

• The phrase “anti cancer” should be written as one word: “anticancer.”

• Also, the word “basidicarps” appears to be misspelled — the correct term is “basidiocarps.”

Missing articles (a / the):

There are a couple of places where the article “a” is missing. For example:

• “...a previous study of Jiao and coworkers (2013)”

• “...as a potential inhibitor of anti-breast cancer targets”

Adding these will improve the flow and readability of the text.

These are all minor fixes that don’t impact the science in any way. Once these are addressed, I believe the manuscript will be ready for acceptance.

Reviewer #2: This study has several notable strengths. It reports Ganoderma ellipsoideum in Vietnam for the first time, confirmed through both morphological characterization and molecular phylogenetic analysis, thereby expanding the known distribution and taxonomy of the species. The work integrates taxonomy, in vitro cytotoxicity testing, and in silico molecular docking, linking biodiversity research to pharmacological potential. The focus on well-established breast cancer–related targets (HPA, MELK, CK2α, NUDT5) enhances biomedical relevance, and the identification of triterpenoids with predicted binding affinities exceeding that of tamoxifen highlights promising anticancer potential. The study also provides transparent sequence data deposition and applies statistical rigor, laying a strong foundation for future compound isolation, mechanistic work, and in vivo validation.

At the same time, several limitations should be acknowledged. Cytotoxicity was assessed only in a single breast cancer cell line (MCF-7) without comparison to normal cells, preventing evaluation of cancer selectivity. The findings are based solely on in vitro assays and in silico predictions, with no in vivo validation or direct biochemical confirmation of the predicted targets. The active compounds were not isolated or quantified from the tested fractions, and their individual contributions to the observed cytotoxicity remain unverified. Chemical composition of extracts was not characterized, and results may vary with different extraction batches or environmental conditions of fungal growth. Docking and ADMET analyses were predictive only and may not reflect biological behavior in living systems. Finally, the study is based on specimens collected from a single location, which may limit generalizability to other populations.

Given these limitations, the conclusions should be presented more modestly, or supported by additional experiments in future work. Specifically, including multiple cancer cell lines, incorporating non-transformed control cells to assess selectivity, and performing direct biochemical confirmation of predicted molecular targets, such as via western blotting, would strengthen the link between molecular docking predictions and observed biological activity.

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-->6. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy .-->

Reviewer #1: No

Reviewer #2: No

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While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/ . PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org . Please note that Supporting Information files do not need this step.

Taxonomic Characterization and Cytotoxic Potential of Vietnamese Ganoderma ellipsoideum Against Human Breast Cancer MCF-7 Cells

PONE-D-25-37431R1

Dear Dr. Tran,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager®  and clicking the ‘Update My Information' link at the top of the page. For questions related to billing, please contact billing support .

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Muhammad Zeeshan Bhatti, Ph.D

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

-->Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.-->

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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-->2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. -->

Reviewer #1: Yes

Reviewer #2: Yes

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-->3. Has the statistical analysis been performed appropriately and rigorously? -->

Reviewer #1: Yes

Reviewer #2: N/A

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-->4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.-->

Reviewer #1: Yes

Reviewer #2: Yes

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-->5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.-->

Reviewer #1: Yes

Reviewer #2: Yes

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-->6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)-->

Reviewer #1: The authors have addressed all comments clearly and thoroughly. The revisions improved the manuscript, and I have no further concerns.

Reviewer #2: Documenting the first confirmed occurrence of Ganoderma ellipsoideum in Vietnam, the study supports this claim with both morphological description and molecular phylogenetic analysis, thereby expanding the species’ known taxonomy and geographic range. By combining taxonomic work with in vitro cytotoxicity assays and in silico molecular docking, the research links biodiversity investigation to pharmacological discovery. Focusing on well-established breast cancer targets (HPA, MELK, CK2α, and NUDT5) strengthens the biomedical relevance, and the identification of triterpenoids whose predicted binding affinities exceed that of tamoxifen points to promising anticancer candidates. Public deposition of sequence data and the application of appropriate statistical methods enhance reproducibility and provide a solid platform for future compound isolation, mechanistic studies, and in vivo validation.

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-->7. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy .-->

Reviewer #1: No

Reviewer #2: No

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