Oleocanthal Induces Mitochondrial Dysfunction in Breast Cancer Cell Lines Depending on c-MET Expression
, Pere Miquel Morla-Barcelo 1,2, Pilar Roca 1,2,3, Jorge Sastre-Serra 1,2,3,* and Mercedes Nadal-Serrano 1,2Round 1
Reviewer 1 Report
The manuscript antioxidants-4149105 entitled "Oleocanthal Induces Mitochondrial Dysfunction in Breast Cancer Cell Lines Depending on c-MET Expression" describes the anticancer effect of oleocanthal in different breast cancer models. The manuscript is interesting and deserves publication after major revisions as detailed below.Major revisions:
-please include a non cancerous cell line (MCF10A) to study the cytotoxicity of the compound.
-please include a control compound to compare the efficacy of the compound (doxorubicin)
-please include the chemical structure of the compound and put in the discussion a relevant comparison with similar compounds.
Author Response
Please see the attachment.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
This manuscript provides a relevant and timely contribution to the current understanding of oleocanthal as an anticancer compound. Although oleocanthal has been widely investigated for its antiproliferative and anti-inflammatory properties, its direct effects on cancer cell metabolism and mitochondrial dynamics have remained insufficiently explored. In this regard, the present study meaningfully expands existing knowledge by identifying mitochondrial dysfunction as a key component of oleocanthal’s mechanism of action in breast cancer cells, particularly in a subtype-dependent context.
Despite these strengths, some limitations should be acknowledged. First, the absence of a reference chemotherapeutic agent used as a positive control limits the ability to directly contextualize the magnitude of oleocanthal-induced effects relative to standard anticancer treatments used in breast cancer. Including such a comparator, or at least explicitly discussing this limitation, would strengthen the translational perspective of the study.
In addition, the concentrations of oleocanthal employed in the in vitro experiments may exceed plasma levels achievable through dietary intake of extra virgin olive oil. This may limit the direct physiological relevance of the findings and should be discussed more explicitly, particularly in the context of potential nutraceutical or therapeutic applications.
Overall, while these considerations do not detract from the scientific merit of the study, addressing them would further enhance its rigor and interpretability.
Finally, the current keywords could be optimized to better reflect the manuscript’s metabolic and mitochondrial focus, as they appear partially redundant with the title. The authors may consider including more specific terms such as mitochondrial dysfunction, cancer metabolism, mitochondrial dynamics, MET signaling, or breast cancer subtypes to improve visibility and indexing.
In the Abstract, subject–verb agreement should be corrected (“remain” to “remains”; Page 1, Lines 23–24). In the Results section, the term “sensible” should be replaced with “sensitive” (Page 6, Lines 214–215), and in the Methods section the incorrect term “lysated” should be corrected to “lysed” (Page 4, Lines 161–162). Redundant punctuation should be removed from the Author Contributions section (“funding acquisition, ," Page 13, Line 487). The phrase “Data is shown” should be corrected to “Data are shown” in figure legends (Page 6, Lines 241–243). Hyphenation in compound modifiers (e.g., oleocanthal-treated, vehicle-treated) should be standardized throughout the manuscript (Pages 5–8). In the list of references, reference 42 is missing the year in bold. Reference 50 is missing the final sheet number (10, "190-."). To review references more quickly, it would be preferable to include the DOI.
Author Response
Please see the attachment.
Author Response File: Author Response.pdf
Round 2
Reviewer 1 Report
no further comments
no further comments
Author Response
Thank you for revising the manuscript.
