Unlocking the Potential of Bioactive Compounds in Pancreatic Cancer Therapy: A Promising Frontier
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThe review “Unlocking the potential of bioactive compounds in pancreatic cancer therapy: a promising frontier” by Silvia Brugiapaglia, Ferdinando Spagnolo and Claudia Curcio is an actual paper about treatment methods for pancreatic ductal adenocarcinoma. It may be accepted for publication after major revision.
Line 131 While preclinical studies have demonstrated that marigold extracts possess anti-tumoral properties against PDA cells – reference is needed.
Line 143 preferential enrichment – ​​explain.
Line 151 In contrast to previous studies - reference is needed where it was increased.
Line 153-172 2.5 Citrus fruits – It is a very modest section, little information about PDA. In fact, only ref. [73]. I would like to see in more detail the results from paragraph 2 refs [57-67], from the general phrase it is not clear what are these papers about. Moreover, citrus fruits are noted to contain flavonoids, and they are discussed in section 2.6. It is necessary to describe in detail the effects on PDA of other biocompounds from citrus fruits, not flavonoids.
Line 211-219 reference is needed in the first paragraph.
Line 232-233 "hispidulin exhibits synergistic anti-tumor effects when combined with 232 some common clinical anticancer drugs" - the phrase is taken from the abstract of work [103] without a link to the original sources, it would be interesting to see them, as well as more detailed information.
Line 262 N is missing – Naringenin.
Line 283 “In cancer” should be delted, because it was done on the cell line.
Line 281-283 "Puerarin has various pharmacological effects, such as enhancing the circulatory system function, reducing myocardial oxygen consumption, decreasing blood sugar, and preventing hypertension and arteriosclerosis [115]" - It would be better to provide references to the original sources, at least something from works 7-9 and 10, perhaps 10 is better, from this work [115].
Line 360-362 «A study found that plasma extracts from individuals consuming anthocyanin-rich juice significantly reduced the migration of PANC-1 cells, though no effect was observed on AsPC-1 cells [138]» - this is not clear, explain.
Line 375 2.6.14 Explain why Xanthohumol, resveratrol, phenethyl isothiocyanate, indole-3-carbinol are in one section.
Refs [172] seems to be not correct.
Line 460 Indicate the cell type “3D cell environment”
Table 1, 2 I would like to see references to publications, if any. Describe the data in the table in more detail. It is not clear how the data in the table is related to the text in lines 502-521.
Line 536-554 – reference is needed.
The discussion and conclusion are the same.
Author Response
Line 131 While preclinical studies have demonstrated that marigold extracts possess anti-tumoral properties against PDA cells – reference is needed.
We added the references as suggested by the Referee
Line 143 preferential enrichment – explain.
We would be grateful to the Referee for their assistance in clarifying the paragraph. The sentence was subsequently rephrased as follows: “While the beneficial effects of polyunsaturated fatty acids (PUFAs) remain a topic of debate in the literature, several studies highlight their antioxidant properties, suggesting a role in enhancing cellular defense mechanisms and inhibiting the arachidonic acid cascade [46]. Conversely, other studies propose that the tumor-suppressive effects of n-3 PUFAs may result from their preferential accumulation in tumor cells. This selective enrichment may render tumor cells more susceptible to oxidative stress and lipid peroxidation, thereby inducing cytotoxic effects and contributing to the inhibition of tumor growth.”
Line 151 In contrast to previous studies - reference is needed where it was increased.
In accordance with the request, three references have been appended to the text. These references detail an increased lipid peroxidation (see new references 47-49).
Line 153-172 2.5 Citrus fruits – It is a very modest section, little information about PDA. In fact, only ref. [73]. I would like to see in more detail the results from paragraph 2 refs [57-67], from the general phrase it is not clear what are these papers about. Moreover, citrus fruits are noted to contain flavonoids, and they are discussed in section 2.6. It is necessary to describe in detail the effects on PDA of other biocompounds from citrus fruits, not flavonoids.
As request, we described more in detail the results of the indicated studies.
Line 211-219 reference is needed in the first paragraph.
We added 3 references as requested (new Ref 100-102).
Line 232-233 "hispidulin exhibits synergistic anti-tumor effects when combined with some common clinical anticancer drugs" - the phrase is taken from the abstract of work [103] without a link to the original sources, it would be interesting to see them, as well as more detailed information.
We added a detailed description of the synergistic effect of hispidulin and the link to original sources as requested.
Line 262 N is missing – Naringenin.
We apologize for the mistake, and we correct it.
Line 283 “In cancer” should be deleted, because it was done on the cell line.
We correct the sentence as indicated.
Line 281-283 "Puerarin has various pharmacological effects, such as enhancing the circulatory system function, reducing myocardial oxygen consumption, decreasing blood sugar, and preventing hypertension and arteriosclerosis [115]" - It would be better to provide references to the original sources, at least something from works 7-9 and 10, perhaps 10 is better, from this work [115].
We indicated the suggested reference.
Line 360-362 «A study found that plasma extracts from individuals consuming anthocyanin-rich juice significantly reduced the migration of PANC-1 cells, though no effect was observed on AsPC-1 cells [138]» - this is not clear, explain.
We explain the different behavior of PDA cells in vitro as indicated.
Line 375 2.6.14 Explain why Xanthohumol, resveratrol, phenethyl isothiocyanate, indole-3-carbinol are in one section.
Due to the limited availability of data, and in order to improve the overall coherence and conciseness of the manuscript, the authors consolidated xanthohumol, resveratrol, phenethyl isothiocyanate, and indole-3-carbinol into a single section.
Refs [172] seems to be not correct.
We apologize for the mistake, and we remove the reference.
Line 460 Indicate the cell type “3D cell environment”
In order to clarify the model employed, the two cell systems utilized were reported.
Table 1, 2 I would like to see references to publications, if any. Describe the data in the table in more detail. It is not clear how the data in the table is related to the text in lines 502-521.
We have added the references to publications in Tables 1 and 2 as suggested. We have also clarified the meaning of these tables in the specified paragraph.
Line 536-554 – reference is needed.
We added the references as indicated (new Ref 198-201).
The discussion and conclusion are the same.
We thank the Referee for the observation. The conclusion section has been revised to clearly distinguish it from the discussion. It now provides a concise summary of the current state of research on bioactive compounds in pancreatic cancer therapy and highlights the need for future clinical validation.
Reviewer 2 Report
Comments and Suggestions for AuthorsThe paper describes the potential of bioactive compounds to prevent or treat the development of pancreatic ductal adenocarcinoma (PDA) which is a highly challenging malignancy to treat. The authors mentioned several classes of bioactive compounds able to target multiple aspects of cancer biology, such as polyphenols, flavonoids, carotenoids and others. The review aims to elucidate the mechanisms by which these bioactive compounds exert their effects, modulating the oxidative stress, influencing inflammatory pathways and regulating cell survival and death. However, a schematic presentation for each such mechanism cited in text would be of great help for the reader to understand the details of the biological activity.
The article is well written and easy to read but another check of typos and spelling is mandatory.
Author Response
The paper describes the potential of bioactive compounds to prevent or treat the development of pancreatic ductal adenocarcinoma (PDA) which is a highly challenging malignancy to treat. The authors mentioned several classes of bioactive compounds able to target multiple aspects of cancer biology, such as polyphenols, flavonoids, carotenoids and others. The review aims to elucidate the mechanisms by which these bioactive compounds exert their effects, modulating the oxidative stress, influencing inflammatory pathways and regulating cell survival and death. However, a schematic presentation for each such mechanism cited in text would be of great help for the reader to understand the details of the biological activity.
We appreciate the referee’s feedback. To improve the clarity and accessibility of our manuscript, we have moved the graphical abstract—originally summarizing the proposed mechanism—into the main body of the text as Figure 1. We believe this change will facilitate understanding for readers of the review by presenting the mechanistic overview at an earlier and more prominent position in the manuscript.
The article is well written and easy to read but another check of typos and spelling is mandatory.
As requested, we revised the full text checking the typos and spelling.
Round 2
Reviewer 1 Report
Comments and Suggestions for AuthorsAccept in present form
