Nanonutraceuticals: Anti-Cancer Activity and Improved Safety of Chemotherapy by Costunolide and Its Nanoformulation against Colon and Breast Cancer
Authors: Shaker A Mousa
Taher A Salaheldin
Amna A Saddiq
Ali H El-Far
Kavitha Godugu
Noureldien H E Darwish
Journal: Biomedicines (2021)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: anticancer; cardiac protection; costunolide; doxorubicin; nanoformulation.

Abstract:  Costunolide (COS) is a sesquiterpene lactone with anticancer properties. The present study investigated the anticancer effects of COS against the human colon (HCT116) and breast (MDA-MB-231-Luc) cancer cell lines. Inhibition of cell lines viability and IC50 of COS were assessed via an MTT assay. Furthermore, the apoptotic rate was detected by assessment of Bcl2-associated X (Bax) and B-cell lymphoma 2 (Bcl2) protein levels by flow cytometry. Xenograft mice model of HCT116 and MDA-MB-231-Luc were carried out to determine the effect of COS and its nanoparticles (COS-NPs). The results demonstrated that COS inhibited the viability of HCT116 and MDA-MB-231-Luc cells, with a half maximal inhibitory concentration value (IC50) of 39.92 µM and 100.57 µM, respectively. COS significantly increased Bax and decreased Bcl2 levels in treated cells. COS and COS-NPs, in combination with doxorubicin (DOX), significantly decreased the tumor growth of HCT116 and MDA-MB-231-Luc implants in mice. Furthermore, oral administration of COS and COS-NPs significantly decreased the viable cells and increased necrotic/apoptotic cells of HCT116 and MDA-MB-231-Luc implants. Interestingly, both COS and COS-NPs protected the cardiac muscles against DOX's cardiotoxicity. The current results indicated the promising anticancer and cardiac muscles protection of COS and COS-NPs when administered with chemotherapy. 

Retracted: No

PubPeer comments:
 Two images in Figure 8D appear unexpectedly similar, except for the bioluminescence signal. *** ![file] ![file] , 
 #1 Please, see the corrected figure in the following link: https: www.mdpi.com 2227-9059 9 8 990 , 
 Please, see the corrected figure in the following link: https: www.mdpi.com 2227-9059 9 8 990 , 
 #2 Please, see the corrected figure in the following link: https: www.mdpi.com 2227-9059 9 8 990 , 
 #4 Thank you. Was this figure corrected, or was I mistaken in identifying the duplicate in the paper? If it was corrected, what accounts for the difference in the fluorescent signatures makes in #1? , 
 #5 Many thanks for your attention. During the proof revision, some mistakes have happened in some images because we draw them by PowerPoint. Immediately, we contacted the editor and sent to him the figures with fluorescence and without fluorescence. After which the editor approved the correct figures that were published in our article. Thanks again. , 
 Dear authors, I have additional concerns: Fig.6(C) contains two histogram plots that look more similar than expected (after horizontal stretching), however, they are not located in the same fluorescence intensity region: ![file] Further, Fig.6(A) and Fig.6(C) contain two histogram plots that look more similar than expected, again, they are not located in the same fluorescence intensity region: ![file] Could the authors please explain this and provide the original FCS files for review, please? , 
 #7 Dear Heterochasta lasioplaca, Greetings! Thank you for your comments. Regarding the FAC area, some drugs as doxorubicin (Dox) induces shift in the histogram because its effect on the fluorescence of the cells. Therefore, we can not did the same area as control samples. Regarding the first two images they are have great differences in shape and width of the histogram (I used the images of same dimensions as the following: https: drive.google.com drive folders 1-wKi2vPcute_JQZiuU6zV_SxDW0ejKky Also, the second images have differences an. Please, see the following link: https: drive.google.com drive folders 1-wKi2vPcute_JQZiuU6zV_SxDW0ejKky , 
 Dear Ali H. El-Far, Thank you for the quick response. Unfortunately, I have to say that the images you provided via google drive do not clarify my concerns as they are practically of the same quality as my screenshots. Still, the histograms are highly similar, which I can tell you as someone who has done flow cytometry for more than 10 years, is very unlikely to happen, especially twice in one data set. Of course, I could be mistaken and I apologize for been so tenacious, but for the sake of scientific integrity, it would be great if you could also upload the original flow cytometry files. (FCS files) so that others could have a look at them to wipe out all concerns. , 
 Although I do not see this mentioned in the paper, the last author appears to be the Editor-in-Chief of this journal. , 
 Yes https: www.mdpi.com journal biomedicines editors #1 Did you find the image irregularities in the pre-proof version? I do not see that this article got a correction... , 
 #11 I don t recall where I found the paper initially, but I think MDPI will sometimes make  stealth corrections. , 
 #12 Actinopolyspora biskrensis, Your comment seems to be unscientific. I chose my word to reply your comment to be a polit and respective scientist. If you have a scientific comment, send it and we will reply. , 
 #11 Dear Heterochasta lasioplaca, Greetings May he see the pre-print. Thanks , 
 #14 How about sharing the FCS files? , 
 #8 Dear author, Please appreciate the likeliness of the FACS plots pointed out in #7 in the animations below. The colors in the second image have been adjusted to appreciate the change. Fig. 6C COS COX+DOX (click to animate) ![file] Fig. 6A and 6C (click to animate) ![file] , 
 #14 Still waiting for the FCS files... ,