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Your manuscript has been reviewed by expert referees, and their critiques are attached below.  I regret to have to inform you that, in its present form, it is not considered suitable for publication in Biol. Pharm. Bull.  Your manuscript has therefore been rejected.

Although, of course, we could give no guarantee of ultimate acceptance at this stage, we would not rule out the possibility of your submitting an entirely new paper with a new number and date of receipt, based on this work, providing you are able to deal with all of the criticisms raised by the reviewers.

If you decide to submit a new manuscript in time, please be sure to attach a separate document (supplemental file) that carefully addresses, point-by-point, the issues raised in the reviewer¡Çs comments.

Comments by Reviewer #1:

The manuscript entitled ¡ÈA novel **, induces apoptosis in MCF-7 cells involving ROS generation and mitochondria activation¡É describes anti-cancer effects and its possible mechanisms of OEL.  Most of the study is well designed, however, there are some problems with interpretation of the data presented.

Major comments:
1) Experimental section should be revised carefully.  In particular, no detailed procedures were shown in ¡ÈMTT assay¡É.  
2) Page 5/Cytotoxicity of OEL in cancer cell lines: Authors claimed ¡ÈOEL had a lower cytotoxicity on normal cells¡É, and reviewer agree partly.  However, in my opinion, OEL can NOT be safe anti-cancer drug because of limited selectivity.  This should be addressed in Discussion section.
3) No efforts have been made to clarify the possible target biomolecules (enzymes, receptors, or other proteins) for OEL, although authors presented a few possible mechanism.  
4) Authors should specify the type of ROS in more detail.
5) It is still unclear why authors made a choice of these tumor and normal cells.  Authors should show rationale(s) for selection.
6) Fig.3: Apoptotic death seemed to be induced without OEL stimulation.  Authors should show the possible reasons.  If it can be natural apoptosis in the cultured cells, the data in Fig. 3 is not in agreement with Fig. 2 partly, since viability of cells without OEL stimulation was found to be 100% even after 72-h treatment.   


Comments by Reviewer #2:

The manuscript by Li et al. is a study of a novel compound (OEL) isolated from Chinese herb
inducing apotosis in MCF-7 cells involving ROS generation and mitochondria activation. In whole, there are of some interest in the current data obtained herein, but these in vitro data seem to be preliminary. In fact, to demonstrate the anti-cancer effect of this compound, the in vivo study should be performed. Thus, the current study has some limitation for the conclusion. If possible, the authors should provide some in vivo data for anti-cancer effect, and the current in vitro data may give the basis for the in vivo data.

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