Phytomedicines Targeting Cancer Stem Cells: Therapeutic Opportunities and Prospects for Pharmaceutical Development
, Mrunmayee Saraff 2, Rekha Gahtori 3, Nidhi Negi 4, Surya Kant Tripathi 5, Jatin Kumar 1, Sanjay Kumar 1, Saad Hamad Aldhayan 6, Sugapriya Dhanasekaran 7, Mosleh Mohammad Abomughaid 7, Kamal Dua 8, Rohit Gundamaraju 9, Shreesh Ojha 10, Janne Ruokolainen 11, Niraj Kumar Jha 12 and Kavindra Kumar Kesari 11,13,*
Round 1
Reviewer 1 Report
The authors should check up carefully the structures of compounds (for ex, there is a mistake in the structure of betulinic acid and excess letter “B” (Figure 3).
Author Response
Reviewer 1
The authors should check up carefully the structures of compounds (for ex, there is a mistake in the structure of betulinic acid and excess letter “B” (Figure 3).
Author Response: We are thankful to the reviewer for providing the critical inputs on our manuscript. As suggested by the reviewer, we have carefully checked the chemical structures of all phytocompounds given in Figure 3. Also, we have corrected the structure of betulinic acid and removed the excess letter B.
Reviewer 2 Report
The review written by Piyush Kumar Gupta and co-workers reports and summarizes the preclinical studies on the effects of phytocompounds on drug-resistant cells isolated from various tumor. Authors wrote very solid and interesting paper. The review is orgenised and well considern. However I think paper needs editing of English language and style required. I am also not fan of figures attached in the text. I suggest tAuthors provide more profesional figures 1 and 2. After this changes I recommend this paper for publication in Pharmaceuticals.
Author Response
We have revised the manuscript as per reviewer suggestions. Now, we think that through this review process, the paper has been improved significantly. The responses addressing each of the comments can be seen below and the suggested changes are incorporated in track change mode along with clean copy of the manuscript.
Reviewer 2
The review written by Piyush Kumar Gupta and co-workers reports and summarizes the preclinical studies on the effects of phytocompounds on drug-resistant cells isolated from various tumor. Authors wrote very solid and interesting paper. The review is organised and well consider. However, I think paper needs editing of English language and style required. I am also not fan of figures attached in the text. I suggest Authors provide more professional figures 1 and 2. After these changes I recommend this paper for publication in Pharmaceuticals.
Author Response: We thank to the reviewer for reviewing our manuscript. Based on the reviewer’s recommendation, we havedone the English language editing (by professional) and changed their style in the manuscript. Also, we have included the professional figures 1 and 2 in the manuscript.
Reviewer 3 Report
The Authors reviewed the preclinical studies on anticancer phytomedicines.
The active compounds that can be found in the plants often have an impact on the metabolism of the other drugs, when they are concomittantly administered. This leads to the pharmacokinetic interaction. Did Authors find any data about such interactions? Can the compounds mentioned in the manuscript interfere with the other drug used in the anticancer therapy?
Author Response
We have revised the manuscript as per reviewer suggestions. The responses addressing each of the comments can be seen below and the suggested changes are incorporated in track change mode along with clean copy of the manuscript.
Reviewer 3
The Authors reviewed the preclinical studies on anticancer phytomedicines. The active compounds that can be found in the plants often have an impact on the metabolism of the other drugs, when they are concomitantly administered. This leads to the pharmacokinetic interaction. Did Authors find any data about such interactions? Can the compounds mentioned in the manuscript interfere with the other drug used in the anticancer therapy?
Author Response: We thank to the reviewer for providing the critical inputs on our manuscript and asking an important point regarding the pharmacokinetic interactions between the drug and phytocompounds. We have gone through all the cited papers in our manuscript where we discussed in brief about the combinatorial therapeutic effects of phytocompounds with chemotherapeutic drugs. We observed that authors did not discuss the pharmacokinetic study in their work and no data was shown in their papers related to the pharmacokinetic interaction. However, they concluded that most of the phytocompounds sensitize drug-resistant cancer cells or cancer stem cells by blocking P-glycoproteins, ABCG receptors, or various cellular signaling pathways so that chemotherapeutic drugs can kill or induce the programmed cell death in these cells. Further, they listed their synergistic anticancer effects on drug resistant cancer cells. However, they did not report anything related to the role of phytocompounds in interfering to the pharmacological action of anticancer therapeutic drugs. Hence, in our manuscript, no reports are available on the listed phytocompounds showing an interreference with the other drugs used in the anticancer therapy.
