{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:08:09Z","timestamp":1772168889964,"version":"3.50.1"},"update-to":[{"DOI":"10.12688\/f1000research.158563.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000}}],"reference-count":52,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100022965","name":"Ministerio de Ciencia, Tecnolog\u00eda e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["923-2019"],"award-info":[{"award-number":["923-2019"]}],"id":[{"id":"10.13039\/100022965","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns5:p>\n                    Background Gastric cancer is the fifth most common cancer and the third leading cause of cancer deaths worldwide. Perioperative or adjuvant chemotherapy improves survival in patients with stage 1B or higher cancers.\n                    <ns5:italic>Moringa oleifera<\/ns5:italic>\n                    and\n                    <ns5:italic>Plukenetia volubilis<\/ns5:italic>\n                    (Sacha inchi) have been reported to enhance various biological functions, including antitumor and antiproliferative activity. Methods In order to evaluate this potential present in crude extracts of the leaves of these plants, as well as the seed oil of\n                    <ns5:italic>P.volubilis<\/ns5:italic>\n                    , the antitumor activity was determined according to the effect of these derivatives on different biological parameters such as cytotoxicity, proliferation, cell cycle, apoptosis (among others), in AGS cells (CRL-1739). Results All extracts tested were cytotoxic at 90 and 160 \u03bcg\/ml concentrations\n                    <ns5:italic>. P. volubilis<\/ns5:italic>\n                    seed oil showed 95% mortality at 1% concentration (CC\n                    <ns5:sub>50<\/ns5:sub>\n                    = 46.7%). Cell proliferation was inhibited, and all extracts affected the cell cycle, but the\n                    <ns5:italic>P. volubilis<\/ns5:italic>\n                    oil significantly induced an accumulation of AGS cells in the sub G1 phase, inducing DNA fragmentation as a mechanism of cell death. The ethanolic\n                    <ns5:italic>M. oleifera<\/ns5:italic>\n                    leaf extract also inhibited cell migration. Conclusion\n                    <ns5:italic>M. oleifera<\/ns5:italic>\n                    ,\n                    <ns5:italic>P. volubilis<\/ns5:italic>\n                    leaf extracts and\n                    <ns5:italic>P. volubilis<\/ns5:italic>\n                    seed oil can potentially be antitumor products. Further validation in a murine model of gastric cancer is needed to investigate the antitumor potential of these extracts further and to continue the development of herbal products that can help in the management of this type of tumor.\n                  <\/ns5:p>","DOI":"10.12688\/f1000research.158563.2","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T05:41:15Z","timestamp":1748324475000},"page":"194","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["In vitro antitumor capacity of extracts obtained from the plants Plukenetia volubilis (Sacha inchi) and Moringa oleifera in gastric cancer"],"prefix":"10.12688","volume":"14","author":[{"given":"Jose","family":"Vargas","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia","family":"Arbelaez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denny","family":"Cardenas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Murillo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria","family":"Ospina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Robledo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4786-3431","authenticated-orcid":false,"given":"Javier","family":"Soto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2025,5,27]]},"reference":[{"key":"ref2","doi-asserted-by":"publisher","first-page":"e0135814","DOI":"10.1371\/journal.pone.0135814","article-title":"Moringa oleifera as an anti-cancer agent against breast and colorectal cancer cell lines.","volume":"10","author":"A Al-Asmari","year":"2015","journal-title":"PLoS One."},{"key":"ref3","first-page":"1828-1837","article-title":"Association of phytol with toxic and cytotoxic activities in an antitumoral perspective: a meta-analysis and systemic review.","volume":"18","author":"M Alencar","year":"2018","journal-title":"Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents)."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"113166","DOI":"10.1016\/j.jep.2020.113166","article-title":"In vitro and in vivo inhibition of HCT116 cells by essential oils from bark and leaves of Virola surinamensis (Rol. ex Rottb.) Warb.(Myristicaceae).","volume":"262","author":"T Anuncia\u00e7ao","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"684","DOI":"10.3390\/ijms21020684","article-title":"Natural polyphenols targeting senescence: A novel prevention and therapy strategy for cancer.","volume":"21","author":"Y Bian","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1216-1222","DOI":"10.1080\/01635581.2015.1087042","article-title":"Beta-sitosterol: a promising but orphan nutraceutical to fight against cancer.","volume":"67","author":"M Bin Sayeed","year":"2015","journal-title":"Nutr. Cancer."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"253-266","DOI":"10.17113\/ftb.59.03.21.6683","article-title":"Biological activity of sacha inchi (Plukenetia volubilis Linneo) and potential uses in human health: A review.","volume":"59","author":"D C\u00e1rdenas","year":"2021","journal-title":"Food Technol. Biotechnol."},{"key":"ref9","first-page":"317-330","article-title":"Low cytotoxicity, and antiproliferative activity on cancer cells, of the plant Senna alata (Fabaceae).","volume":"69","author":"A Chahardehi","year":"2021","journal-title":"Rev. Biol. Trop."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"6598-6602","DOI":"10.1016\/j.bmc.2010.03.057","article-title":"Potential anti-inflammatory phenolic glycosides from the medicinal plant Moringa oleifera fruits.","volume":"18","author":"S Cheenpracha","year":"2010","journal-title":"Bioorg. Med. Chem."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"20","DOI":"10.3390\/plants13010020","article-title":"Bioactive compounds in Moringa oleifera: mechanisms of action, focus on their anti-inflammatory properties.","volume":"13","author":"A Chi\u0219","year":"2023","journal-title":"Plants."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"1732-1739","DOI":"10.1016\/j.foodchem.2013.04.078","article-title":"Sacha inchi (Plukenetia volubilis): A seed source of polyunsaturated fatty acids, tocopherols, phytosterols, phenolic compounds and antioxidant capacity.","volume":"141","author":"R Chirinos","year":"2013","journal-title":"Food Chem."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"41-59","DOI":"10.1159\/000443404","article-title":"Natural products as a vital source for the discovery of cancer chemotherapeutic and chemopreventive agents.","volume":"25","author":"G Cragg","year":"2016","journal-title":"Med. Princ. Pract."},{"key":"ref13","article-title":"Anticancer Effect of Moringa oleifera Leaf Extract in Human Cancer Cell Lines.","volume":"9","author":"M Del Mar Zayas-Viera","year":"2016","journal-title":"J. Health Dispar. Res. Pract."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"281-287","DOI":"10.1007\/s12231-019-09459-y","article-title":"Ethnobotanical knowledge in the peruvian amazon of the neglected and underutilized crop Sacha Inchi (Plukenetia volubilis L.).","volume":"73","author":"A del-Castillo","year":"2019","journal-title":"Econ. Bot."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"687-699","DOI":"10.1111\/j.1751-7915.2010.00221.x","article-title":"Natural products for cancer chemotherapy.","volume":"4","author":"A Demain","year":"2011","journal-title":"Microb. Biotechnol."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"191-198","DOI":"10.5513\/JCEA01\/26.1.4400","article-title":"Optical analysis, antioxidant activity and microbiological quality of cold-pressed pumpkin oil.","volume":"26","author":"V \u0110urovi\u0107","year":"2025","journal-title":"J. Cent. Eur. Agric."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"112248","DOI":"10.1016\/j.biopha.2021.112248","article-title":"Antioxidant and antiproliferative potential of ethanolic extracts from Moringa oleifera, Tropaeolum tuberosum and Annona cherimola in colorrectal cancer cells.","volume":"143","author":"M Fuel","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"7621-7630","DOI":"10.1002\/jsfa.12845","article-title":"Peptide fractions from Sacha inchi induced apoptosis in HepG2 cells via P53 activation and a mitochondria-mediated pathway.","volume":"103","author":"Z He","year":"2023","journal-title":"J. Sci. Food Agric."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"115968","DOI":"10.1016\/j.bmc.2020.115968","article-title":"Fluorescent image-based high-content screening of extracts of natural resources for cell cycle inhibitors and identification of a new sesquiterpene quinone from the sponge, Dactylospongia metachromia.","volume":"31","author":"Y Hitora","year":"2021","journal-title":"Bioorg. Med. Chem."},{"key":"ref19","first-page":"8467-8471","article-title":"Active principle from Moringa oleifera Lam leaves effective against two leukemias and a hepatocarcinoma.","volume":"9","author":"M Khalafalla","year":"2010","journal-title":"Afr. J. Biotechnol."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1193-1206","DOI":"10.1080\/01635581.2020.1792517","article-title":"Antitumor activity of ethanolic extract from Thymbra spicata L. aerial parts: effects on cell viability and proliferation, apoptosis Induction, STAT3, and NF-kB signaling.","volume":"73","author":"M Khalil","year":"2021","journal-title":"Nutr. Cancer."},{"key":"ref21","first-page":"68-82","article-title":"Antitumor activity of Moringa oleifera leaf extract against Ehrlich solid tumor.","volume":"4","author":"W Khalil","year":"2014","journal-title":"Int. J. Pharm."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1071243","DOI":"10.1155\/2018\/1071243","article-title":"The in vitro and in vivo anticancer properties of Moringa oleifera.","volume":"2018","author":"K Khor","year":"2018","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.3390\/agronomy11061066","article-title":"Sacha inchi (Plukenetia volubilis L.) is an underutilized crop with a great potential.","volume":"11","author":"N Kodahl","year":"2021","journal-title":"Agronomy."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1-11","DOI":"10.1186\/1477-7819-11-118","article-title":"Nitric oxide and cancer: a review.","volume":"11","author":"S Korde Choudhari","year":"2013","journal-title":"World J. Surg. Oncol."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"803-812","DOI":"10.1016\/j.jep.2011.01.035","article-title":"Cytotoxicity of some Cameroonian spices and selected medicinal plant extracts.","volume":"134","author":"V Kuete","year":"2011","journal-title":"J. Ethnopharmacol."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"265-267","DOI":"10.1242\/jcs.01610","article-title":"Death receptor signaling.","volume":"118","author":"I Lavrik","year":"2005","journal-title":"J. Cell Sci."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"4672","DOI":"10.3390\/molecules25204672","article-title":"Extraction processes with several solvents on total bioactive compounds in different organs of three medicinal plants.","volume":"25","author":"N Lezoul","year":"2020","journal-title":"Molecules."},{"key":"ref27","first-page":"1420-1425","article-title":"Stigmasterol exhibits potent antitumor effects in human gastric cancer cells mediated via inhibition of cell migration, cell cycle arrest, mitochondrial mediated apoptosis and inhibition of JAK\/STAT signalling pathway.","volume":"23","author":"K Li","year":"2018","journal-title":"J. BUON."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1-32","DOI":"10.1186\/s12885-015-1101-8","article-title":"Prediction of resistance to chemotherapy in ovarian cancer: a systematic review.","volume":"15","author":"K Lloyd","year":"2015","journal-title":"BMC Cancer."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"566","DOI":"10.3390\/nu13020566","article-title":"Antitumor effect of the ethanolic extract from seeds of Euphorbia lathyris in colorectal cancer.","volume":"13","author":"C Mesas","year":"2021","journal-title":"Nutrients."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"984-989","DOI":"10.1111\/j.1349-7006.2006.00289.x","article-title":"Genetic instability in cancer cells by impaired cell cycle checkpoints.","volume":"97","author":"M Nakanishi","year":"2006","journal-title":"Cancer Sci."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1-10","DOI":"10.1155\/2013\/950272","article-title":"Antioxidant and antiproliferative activities of leaf extracts from Plukenetia volubilis Linneo (Euphorbiaceae).","volume":"2013","author":"A Nascimento","year":"2013","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"770-803","DOI":"10.1021\/acs.jnatprod.9b01285","article-title":"Natural products as sources of new drugs over the nearly four decades from 01\/1981 to 09\/2019.","volume":"83","author":"D Newman","year":"2020","journal-title":"J. Nat. Prod."},{"key":"ref33","first-page":"1840-1845","article-title":"Cycloartenol exerts anti-proliferative effects on Glioma U87 cells via induction of cell cycle arrest and p38 MAPK-mediated apoptosis.","volume":"23","author":"H Niu","year":"2018","journal-title":"J. BUON."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"304-316","DOI":"10.1016\/j.sajb.2019.08.021","article-title":"An updated comprehensive review of the medicinal, phytochemical and pharmacological properties of Moringa oleifera.","volume":"129","author":"B Padayachee","year":"2020","journal-title":"S. Afr. J. Bot."},{"key":"ref35","article-title":"Cytotoxic effect of Moringa oleifera leaf extracts on human multiple myeloma cell lines.","author":"M Parvathy","year":"2007"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"3787","DOI":"10.3390\/foods11233787","article-title":"A comprehensive review of Moringa oleifera bioactive compounds\u2014cytotoxicity evaluation and their encapsulation.","volume":"11","author":"O Pop","year":"2022","journal-title":"Foods."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"4503-4515","DOI":"10.1007\/s13197-019-03938-9","article-title":"Characterization of commercial Sacha inchi oil according to its composition: tocopherols, fatty acids, sterols, triterpene and aliphatic alcohols.","volume":"56","author":"F Ramos-Escudero","year":"2019","journal-title":"J. Food Sci. Technol."},{"key":"ref37","first-page":"1311-1316","article-title":"Enhanced cisplatin cytotoxicity by disturbing the nucleotide excision repair pathway in ovarian cancer cell lines.","volume":"63","author":"M Selvakumaran","year":"2003","journal-title":"Cancer Res."},{"key":"ref56","first-page":"93-103","article-title":"Extract from Moringa oleifera seeds suppresses the epithelial-mesenchymal transition-mediated metastasis of gastric cancer by targeting the metastatic suppressor NDRG1.","volume":"50","author":"X Shu","year":"2018","journal-title":"J. Funct. Foods."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1270-1275","DOI":"10.1016\/j.fct.2011.03.006","article-title":"Antiproliferation and induction of apoptosis by Moringa oleifera leaf extract on human cancer cells.","volume":"49","author":"S Sreelatha","year":"2011","journal-title":"Food Chem. Toxicol."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"209-249","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.","volume":"71","author":"H Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"398-403","DOI":"10.1089\/jmf.2015.0113","article-title":"The antiproliferative effect of Moringa oleifera crude aqueous leaf extract on human esophageal cancer cells.","volume":"19","author":"C Tiloke","year":"2016","journal-title":"J. Med. Food."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"1-8","DOI":"10.1186\/1472-6882-13-226","article-title":"The antiproliferative effect of Moringa oleifera crude aqueous leaf extract on cancerous human alveolar epithelial cells.","volume":"13","author":"C Tiloke","year":"2013","journal-title":"BMC Complement. Altern. Med."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"1-9","DOI":"10.1155\/2019\/8178294","article-title":"Evaluation of the use of different solvents for phytochemical constituents, antioxidants, and in vitro anti-inflammatory activities of Severinia buxifolia.","volume":"2019","author":"D Truong","year":"2019","journal-title":"J. Food Qual."},{"key":"ref50","doi-asserted-by":"publisher","DOI":"10.5772\/intechopen.96690","article-title":"Sacha Inchi Seed (Plukenetia volubilis L.) Oil: Terpenoids.","volume":"35","author":"A Valencia","year":"2021","journal-title":"Terpenes and Terpenoids: Recent Advances."},{"key":"ref42","doi-asserted-by":"publisher","DOI":"10.6084\/m9.figshare.27317220.v1","volume":"2024","author":"J Vargas","year":"2024","journal-title":"figshare."},{"key":"ref43","first-page":"11-13","article-title":"The combinatorial chemistry of nature.","volume":"384","author":"G Verdine","year":"1996","journal-title":"Nature."},{"key":"ref1","article-title":"Global cancer burden growing, amidst mounting need for services.","year":"2024"},{"key":"ref44","article-title":"Total phenolic, flavonoid, flavonol contents and antioxidant activity of Inca peanut (Plukenetia volubilis L.) leaves extracts.","author":"N Wuttisin","year":"2021"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"296","DOI":"10.3390\/antiox8080296","article-title":"Antioxidant and anti-inflammatory activities of the crude extracts of Moringa oleifera from Kenya and their correlations with flavonoids.","volume":"8","author":"Y Xu","year":"2019","journal-title":"Antioxidants."},{"key":"ref55","first-page":"94-106","article-title":"Mode of action of a formulation containing hydrazones and saponins against leishmania spp. Role in mitochondria, proteases and reinfection process.","volume":"13","author":"Y Zapata","year":"2020","journal-title":"Int. J. Parasitol. 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We are grateful for the useful comments and constructive feedback, which have helped us to improve the clarity, rigor, and impact of our work.  We have carefully considered all the suggestions and have made the necessary revisions accordingly. Below, we provide a detailed response to each comment, highlighting the changes made to the manuscript. For clarity, we present the reviewers' comments in bold, followed by our responses in regular text. In cases where substantial modifications were made, we indicate the corresponding changes in the revised manuscript.  \n<b>Introduction The sentence below is not relevant to the article.&nbsp; &quot;Between 1971 and 2007, an increase in survival of only 17% has been achieved in ovarian cancer (<\/b>\n<b>Lloyd, Cree, &amp; Savage, 2015<\/b>\n<b>), while in breast cancer, the increase has been 38% in 10-year survival.&quot;<\/b> Response: We agree with this observation. Text was removed from the document.  \n<b>Methods 1- The spelling of roto evaporation should be checked.<\/b> \n<i>Response: Corrected<\/i>  \n<b>2-&nbsp;In the method section, using dots and commas in numbers should be checked.<\/b> \n<i>Response: Revised and corrected<\/i>  \n<b>3- Space usage should be corrected (for example, &quot;100<\/b>\n<b>\u03bc<\/b>\n<b>l in each well. 20<\/b>\n<b>\u03bc<\/b>\n<b>l\/....&quot;.).<\/b> \n<i>Response: Revised and corrected.<\/i>  \n<b>4-&nbsp;Why were different concentrations used for cell cytotoxicity and cell proliferation?<\/b>  \n<i>Response: We consider it inadequate to evaluate the same concentrations since cytotoxicity and cell proliferation are distinct events. Cytotoxicity assays assesses cell damage or death, whereas proliferation measures cell growth and replication. A concentration that induces cytotoxicity may not be the same as one that affects proliferation.  When we adapt the concentration range based on the effect being studied, we can obtain more precise and relevant information while also enabling the establishment of a dose-response curve. This helps to identify the minimum effective concentration and the maximum tolerable dose, optimizing the interpretation of the extract\u2019s effects. In some cases, some concentrations may stimulate cell proliferation instead of inducing toxicity, so evaluating different ranges allows for determining optimal conditions to maximize the desired effect.  Some concentrations may inhibit proliferation without causing cytotoxicity, whereas others may stimulate cell growth without significant damage. Therefore, depending on the study's objectives, it is recommended to use a broader range for cytotoxicity assessment and a more specific range for cell proliferation to obtain clearer results.  Adjusting the concentration range according to the type of evaluation (cytotoxicity or proliferation) enables the collection of more precise and reproducible data, improving result interpretation and its applicability in future research. In our work, initially a range of concentrations was used to identify the CC50 in the cytotoxicity tests, but later in the proliferation assays the concentrations were in ranges lower than the CC50 because we wanted to evaluate if lower concentrations could have an antiproliferative effect when the cells are treated for a longer time, as it happens in the proliferation assays compared to the cytotoxicity assays. In fact, proliferation assays are usually performed with a single dose, but we wanted to demonstrate the effect already described<\/i>.  \n<b>5- Spelling errors must be corrected (for example, H2DCFDA).<\/b> \n<i>Response: revised and corrected<\/i>  \n<b>6- What is the ON production?<\/b> \n<i>Response: ON means nitric oxide. There was a spelling mistake. Now was revised and corrected.<\/i>  \n<b>Results 1- The acronym for NO should be given<\/b> \n<i>Response: Acronym for NO was given in text.<\/i>  \n<b>2-&nbsp;The explanation of Table 2 is insufficient.&nbsp;What is meant by C- or C+?<\/b> \n<i>Response: The table and explanation have been modified<\/i>  Treatment&nbsp;&nbsp; &nbsp;ROS&nbsp;&nbsp; &nbsp;ON Negative control &nbsp;&nbsp; &nbsp;29.3 &plusmn; 2,6&nbsp;&nbsp; &nbsp;22.3 &plusmn; 1.7 Positive control &nbsp;&nbsp; &nbsp;63.1 &plusmn; 13.6 (\u2191 2.1 x)&nbsp;&nbsp; &nbsp;58.3 &plusmn; 6.5 (\u2191 2.6 x) P. volubilis oil&nbsp;&nbsp; &nbsp;46.7 &plusmn; 10.8 (\u2191 1.6 x) &nbsp;&nbsp; &nbsp;50.1 &plusmn; 2.7 (\u2191 2.2 x)  Data show the mean &plusmn; SD of the percentage of cells positive for ROS and NO without treatment (Negative control), treated with PHA to induce ROS production, or PMA to induce NO production (Positive control), and treated with \n<i>P. volubilis<\/i> seed oil. Arrows \u2191\u2193 represent the increase or decrease concerning the untreated basal condition.   \n<b>3- Why was only&nbsp;<i>Plukenetia Volubilis<\/i>&nbsp;seed oil examined in the ROS experiment, and why were other extracts not analyzed?<\/b> \n<i>Response: This approach specifically focused on Plukenetia volubilis oil, as this derivative was exhibiting promising characteristics at that stage of the research, particularly in terms of toxicity, antiproliferative effects, caspase activation, and cell cycle arrest. Additionally, the decision to explore this oil was reinforced by the lack of prior studies on its role in inducing metabolic stress in cancer.<\/i>  \n<b>4-&nbsp;Which extract was used in the wound closure test (Figure 8)? Why are there no other extract results analyzed in the study?<\/b> \n<i>Response: As indicated in the results, the ethanol extract of Moringa oleifera was used in the wound closure test (Figure 8). This was the only extract analyzed in the study because it was the only one that exhibited notable antimigratory activity in the treated cells.<\/i>  \n<b>5-&nbsp;All figure descriptions must specify the extracts and their respective concentrations used in the experiment.<\/b> \n<i>Response: The required information was added.<\/i>  \n<b>6-&nbsp;In all analyses, all extracts used in the study must be included, or the reason why they were not used must be explained in detail.<\/b> \n<i>Response: This concern were addressed in questions 3 and 4. Please see above.<\/i>  \n<b>Discussion&nbsp; 1- An article (Shu X, et al., 2018 [Ref 1]) examining the effects of&nbsp;<i>Moringa oleifera<\/i>&nbsp;extracts on gastric cancer and its metastasis should be included in the discussion section and discussed.<\/b> Response: We added this paragraph:  \n<i>However, further studies are needed to establish whether the cells are incited by the action of the extracts to follow an apoptotic or antimetastatic pathway, such as a reversal of the epithelial-mesenchymal transition in gastric cancer cells. In an approach similar to that performed in our study, Shu X et al (2018) were able to demonstrate at the cellular and molecular level the hypothesis related to the reversal of epithelial-mesenchymal transition. In that work, extracts from M. oleifera seed were evaluated, and through migration and invasion assays the anti-metastatic potential in gastric cancer cells was evidenced, also revealing the possible cellular target of the extract, since a positive regulation of NDRG1 expression was observed in the treated cells <\/i>\n<i>(Shu et al., 2018)<\/i>\n<i>, which is a gene with invasion and metastasis suppressor activity. Based on this evidence, gene expression assays or protein analysis could be performed in the cells treated with our extract, contemplating not only the evaluation of NDRG1 but also other reversion markers such as ZO-1 and vimentin, among others.<\/i>","URL":"https:\/\/f1000research.com\/articles\/14-194\/v2#referee-comment-13542","order":1,"name":"referee-comment-13542","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.174174.r375096, Hassan A. Alshamsi, University of Al-Qadisiyah, Al Diwaniyah, 15 Apr 2025, version 1, 3 approved with reservations","URL":"https:\/\/f1000research.com\/articles\/14-194\/v1#referee-response-375096","order":2,"name":"referee-response-375096","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.182185.r387433, Abdul Mueed, Nanjing Agricultural University, Nanjing, 28 May 2025, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/14-194\/v2#referee-response-387433","order":3,"name":"referee-response-387433","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This study was financially supported by the Colombian Ministry of Science and Technology (MINCIENCIAS) under contract 923-2019. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":4,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}