Submited on: 11 Sep 2010 07:55:00 AM GMT
Published on: 12 Sep 2010 12:19:24 AM GMT
 

1 Is the subject of the article within the scope of the subject category? Yes
2 Are the interpretations / conclusions sound and justified by the data? Yes
3 Is this a new and original contribution? Yes
4 Does this paper exemplify an awareness of other research on the topic? Yes
5 Are structure and length satisfactory? Yes
6 Can you suggest brief additions or amendments or an introductory statement that will increase the value of this paper for an international audience? Yes
7 Can you suggest any reductions in the paper, or deletions of parts? No
8 Is the quality of the diction satisfactory? Yes
9 Are the illustrations and tables necessary and acceptable? Yes
10 Are the references adequate and are they all necessary? Yes
11 Are the keywords and abstract or summary informative? Yes
  • Other Comments:


    This paper provides in vitro anti-cancer studies of a series of compounds derived from natural herb that is is commonly used in the Kempo medicine. The study was done in a detail manner focussing primarily on the anti-telomerase activity.The paper could be improved in a number of ways. 1) The sourcing of the materials should be more clearly identified. It is common knowledge that herbs tend to vary in their phytochemical conditions based on their variety and planting conditions.

     

    The IC50 values of each compound should be tabulated in a table. The IC50 values can provide better insight into the anticancer potential of  the compounds. The author did mention that the antiproliferative activity was mild (unpublished data) such indication would have given a clue that most likely the compounds will not target the toposiomerase activity. Compounds that targets topoisomerase enzymes tend to have strong cytotoxic response.

     

    Overall, the paper provides a good insight into the anti-cancer activity of these compounds. However, to stress on cancer preventative properties , one must also look at other pathways such as angiogenesis. Many natural products appear to confer their anti cancer activity via this pathway instead of the cytotoxic pathway.

     

  • Competing interests:
    none
  • Invited by the author to review this article? :
    No
  • Have you previously published on this or a similar topic?:
    Yes
  • References:
    Aisha, Abdalrahim F. A., Zeyad D. Nassar, Mohammad J. Siddiqui, Khalid M. Abu-Salah, Salman A. Alrokayan, Zhari Ismail, Amin Malik Shah Abdul Majid. 2011, Evaluation of Antiangiogenic, Cytotoxic and Antioxidant Effects of Syzygium aromaticum L Extracts. Asian Journal of Biological Sciences 4 (3) 282-290 S. M. S. Omari, S. M. Salhimi, N. N. Muttiah, A. F. A. Aisha, A. M. S. Abdul Majid, I. Mat and A. Abdul Latiff. 2010, Differential Phosphorylation and Expression Events of Focal Adhesion Kinase under Anchorage-dependent and Anchorage-Independent Conditions. Journal of Biological Sciences Helal M, Al-Douh M, Hamid S, Osman H, Salhimi S, AMS Abdul Majid .2010, Diaminobenzene Schiff Base Induces Caspase 9-dependent Apoptosis In U937 Leukemia Cells. Webmed Central 1 (10) WMC001081 Majid AM, Smythe G, Denny WA, Wakelin LP, 2007, Structure of the d(CGCGAATTCGCG)2 complex of the minor groove binding alkylating agent alkamin studied by mass spectrometry.Molecular Pharmacology,71 (4) ,1165-78 Abdul Majid AM, Smythe G, Denny WA, Wakelin LP, 2009, Mass spectrometry studies of the binding of the minor groove-directed alkylating agent alkamin to AT-tract oligonucleotides. Chemical Research In Toxicology, 22 (1), 146-157
  • Experience and credentials in the specific area of science:

    I work on cancer drug discovery from natural products.

  • How to cite:  Abdul Majid A .Preventive impact of alkaloids with anti-cancer effect extracted from natural herb and the derivatives [Review of the article 'Preventive impact of alkaloids with anti-cancer effect extracted from natural herb and the derivatives ' by Hasegawa J].WebmedCentral 2010;1(12):WMCRW00223
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Dear Dr. Amin Malik Shah Abdul Majid, Thank you for your valuable comments. According to your advice, we corrected my manuscript as below. We appreciate you very much. Reviewer’s comment: 1. The authors emphasized that the alkaloids used in the present study had few adverse effects (Please see the Abstract and Conclusions sections.). Nevertheless, the present study lacks in vivo experiments. I suppose that an adverse effect is generally a harmful and undesired effect resulting from a medication or other intervention such as surgery. The comments are not suitable as conclusions drawn from only in vitro experiment. Rather, in the current setting, the authors should state that the effect of the alkaloids is cancer-specific on the basis of a lack of the anti-proliferative effect on SUSM1 cells without activity of telomerase. Answer:?In Kampo medicine (Japanese traditional herb medicine), as I described in my article, such alkaloids have been used for human body at a physiological concentration and it has been well known that they have few adverse effects. That is why we did not perform in vivo. It is definitely epidemiological study that is needed after the data resulting from my manuscript. In this study, we used alkaloid for mice at the same quantities/kg as for human body. As I described this content in my manuscript, I added “the effect of the alkaloids is cancer-specific on the basis of a lack of the anti-proliferative effect on normal cells such as SUSM cells without activity of telomerase.” in conclusion of abstract, as you instructed in the comments. 2. What`s Kampo medicine? Is it traditional Japanese medicine? Unclear or undefined words must be explained in more detail in order to avoid misleading many readers. Answer: Kampo medicine have been recently known as Japanese traditional herb medicine for clinic and oral use and the definition was published in the following articles. 1) Efficacy of Rikkunshito, a traditional Japanese medicine (Kampo), in treating functional dyspepsia. Kusunoki H, Haruma K, Hata J, Ishii M, Kamada T, Yamashita N, Honda K, Inoue K, Imamura H, Manabe N, Shiotani A, Tsunoda T. Intern Med. 2010;49(20):2195-202. Epub 2010 Oct 15. 2) e traditional Japanese formula keishibukuryogan reduces liver injury and inflammation in patients with nonalcoholic fatty liver disease. Fujimoto M, Tsuneyama K, Kinoshita H, Goto H, Takano Y, Selmi C, Keen CL, Gershwin ME, Shimada Y. Ann N Y Acad Sci. 2010 Mar;1190:151-8. 3) Exodus of Kampo, traditional Japanese medicine, from the complementary and alternative medicines: is it time yet? Kono T, Kanematsu T, Kitajima M. Surgery. 2009 Nov;146(5):837-40. 4) Kampo medicine, based on traditional medicine theory, in treating uncured glossodynia: efficacy in five clinical cases. Hijikata Y, Makiura N, Kano T, Higasa K, Shimizu M, Kawata K, Mine T. Am J Chin Med. 2008;36(5):835-47. In p.4, L.3-5. We are explaining Kampo medicine, only as described in paper 1)-4). This is a definite phrase used for the explanation of Kampo Medicine. Please see the papers above. 3. In the Methods section, the authors used the database of Tsumura Corp. To help readers, the authors should explain the selection step and the Web information in detail. If possible, they should release the information as supplementary data. Answer: We added http://www.saglasie.com/tr/chemical/index.htm; http://moldb.nihs.go.jp/jan/index.aspx; http://moldb.nihs.go.jp/jp/index.aspx; http://www.pharmis.org/index.htm in Methods (p.6, L.12-13), to my manuscript as you pointed out. 4. The authors did not explain the preparation process of the alkaloids. How do the authors prepare the alkaloids? What?s the medium used? Water or, ethyl or methyl alcohol? Answer: We cannot know the details about methodology due to the confidential content in the company. But we added methodology for extracting alkaloids as additional file. In p.6, L4-7, we added as “We screened 23 herbs containing at least one alkaloid, routinely used in Kampo Medicine (Supplementary figure 1) after the extraction with general methods from herbs and a part of plant (Supplementary figure 2) and with tumor suppressive effect after testing their sensitivity” 5. In the Discussion section, the authors stated Approximately 23 herbs used in . This lack of source of the information would mislead reader; therefore, the authors should cite the relevant papers. Answer: We added this information as additional file 1. We added the explanation as ” We screened 23 herbs containing at least one alkaloid, routinely used in Kampo Medicine (Supplementary figure 1) after the extraction with general methods from herbs and a part of plant (Supplementary figure 2)” in p.6. L.4-5. Also, as you know, IC50 of telomerase inhibitors cannot prove and calculate in a routine way to examine the effect of anti-cancer drug because such a drug first induced senescence, followed apoptosis. We believe that Calculating IC50 has no scientific evidence and meaning. So, I am so sorry about this matter.
Responded by Mr. Norimasa Miura on 12 Dec 2010 12:15:15 PM

  • Other Comments: Kabashima et al have answered my questions adequately, and resolved the issues I pointed out.
  • Competing interests:
    No
  • Invited by the author to review this article? :
    Yes
  • Have you previously published on this or a similar topic?:
    No
  • References:
    None
  • Experience and credentials in the specific area of science:
    None
  • How to cite:  Iizuka N .Preventive impact of alkaloids with anti-cancer effect extracted from natural herb and the derivatives [Review of the article 'Preventive impact of alkaloids with anti-cancer effect extracted from natural herb and the derivatives ' by Hasegawa J].WebmedCentral 2010;1(9):WMCRW0044
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  • Other Comments: Minor revise is needed for publication of this article. It seems that scenario of current study on herb or its constituents has two main streams, i.e., an identification of unknown constituents from herbs and an elucidation of molecular basis underlying the action of an herb or its constituents. To address the latter scenario, Kabashima et al have examined the anti-cancer activity of several constituents belonging to alkaloids in both some cancer cell lines and a non malignant cell line SUSM1. Methodologically, the present study has been well performed and well documented; however, it suffers from several drawbacks. The current state is in my opinion not suitable for publication in this journal. 1. The authors emphasized that the alkaloids used in the present study had few adverse effects (Please see the Abstract and Conclusions sections.). Nevertheless, the present study lacks in vivo experiments. I suppose that an adverse effect is generally a harmful and undesired effect resulting from a medication or other intervention such as surgery. The comments are not suitable as conclusions drawn from only in vitro experiment. Rather, in the current setting, the authors should state that the effect of the alkaloids is cancer-specific on the basis of a lack of the anti-proliferative effect on SUSM1 cells without activity of telomerase. 2. What`s Kampo medicine? Is it traditional Japanese medicine? Unclear or undefined words must be explained in more detail in order to avoid misleading many readers. 3. In the Methods section, the authors used the database of Tsumura Corp. To help readers, the authors should explain the selection step and the Web information in detail. If possible, they should release the information as supplementary data. 4. The authors did not explain the preparation process of the alkaloids. How do the authors prepare the alkaloids? What?s the medium used? Water or, ethyl or methyl alcohol? 5. In the Discussion section, the authors stated Approximately 23 herbs used in ??. This lack of source of the information would mislead reader; therefore, the authors should cite the relevant papers.
  • Invited by the author to review this article? :
    Yes
  • Have you previously published on this or a similar topic?:
    Yes
  • References:
    None
  • Experience and credentials in the specific area of science:
    None
  • How to cite:  Iizuka N .Preventive impact of alkaloids with anti-cancer effect extracted from natural herb and the derivatives [Review of the article 'Preventive impact of alkaloids with anti-cancer effect extracted from natural herb and the derivatives ' by Hasegawa J].WebmedCentral 2010;1(9):WMCRW0030
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