Elaeagnus angustifolia Plant Extract Inhibits Epithelial-Mesenchymal Transition and Induces Apoptosis via HER2 Inactivation and JNK Pathway in HER2-Positive Breast Cancer Cells
Authors: Anju Sharma
Hadeel Kheraldine
Ayesha Jabeen
Halema F Al Farsi
Semir Vranic
Ala-Eddin Al Moustafa
Ishita Gupta
Journal: Molecules (2020)
Discipline: CHEMISTRY
Keywords: EMT; Elaeagnus angustifolia; apoptosis; breast cancer; chemoprevention.
Affiliations: College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, Qatar., Biomedical Research Centre, Qatar University, Doha P.O. Box 2713, Qatar., College of Pharmacy, Qatar University, Doha P.O. Box 2713, Qatar.

Abstract:  Elaeagnus angustifolia (EA) is a medicinal plant used for treating several human diseases in the Middle East. Meanwhile, the outcome of EA extract on HER2-positive breast cancer remains nascent. Thus, we herein investigated the effects of the aqueous EA extract obtained from the flowers of EA on two HER2-positive breast cancer cell lines, SKBR3 and ZR75-1. Our data revealed that EA extract inhibits cell proliferation and deregulates cell-cycle progression of these two cancer cell lines. EA extract also prevents the progression of epithelial-mesenchymal transition (EMT), an important event for cancer invasion and metastasis; this is accompanied by upregulations of E-cadherin and β-catenin, in addition to downregulations of vimentin and fascin, which are major markers of EMT. Thus, EA extract causes a drastic decrease in cell invasion ability of SKBR3 and ZR75-1 cancer cells. Additionally, we found that EA extract inhibits colony formation of both cell lines in comparison with their matched control. The molecular pathway analysis of HER2 and JNK1/2/3 of EA extract exposed cells revealed that it can block HER2 and JNK1/2/3 activities, which could be the major molecular pathway behind these events. Our findings implicate that EA extract may possess chemo-preventive effects against HER2-positive breast cancer via HER2 inactivation and specifically JNK1/2/3 signaling pathways. 

Retracted: No

PubPeer comments:
 1. There is an error in Figure 3. 2. Please can the authors provide original gels for the western blot data shown in Figure 7 and 8? A number of proteins are shown and beta-actin is shown as a loading control. Please can the authors clarify if all these proteins were probed in the same membrane such that beta-actin served as a single loading control for all of them? The MW markers are not included, so it is difficult to figure out how the proteins may have been arranged in the blot. Thank you! ![file] ![file] , 
 Figure 7A. * Pink boxes: The b-Catenin and p-b-Catenin panels look more similar to each other than expected if one of them is rotated 180 degrees. * Both panels also look unexpectedly similar to lanes in the E-Cadherin panel in Figure 7B from another paper from the same research group, i.e. Ishita Gupta et al., Frontiers in Oncology (2021), DOI: 10.3389 fonc.2021.630408 - https: pubpeer.com publications 927D5B26698F37C40C89B9199F3BA1 ![file] , 
 Dear Dr. Bik Kindly note that the blots are not twisted or rotated as mentioned. Find the original blots for beta-catenin ![file] and phospho-beta-catenin ![file] . To further inform you, all the original blots have been submitted to the Frontiers in Oncology for the manuscript Ishita Gupta et al., Frontiers in Oncology (2021), DOI: 10.3389 fonc.2021.630408 . However, for your reference the blot has been attached ![file] . I believe the manuscripts have been reviewed by reviewers prior to publication. If any change is required from our side, we shall contact the journal directly for the needful. , 
 #3 Dear author, this is an awkward attempt to mislead the truth: ![file] , 
 #3 Thank you for responding. I presume you are one of the authors. The images you provided here are of low resolution which makes any comparison difficult. It would be appreciated if you would post a link here to an external site (such as Imgur.com or Google Drive) to provide readers access to larger uncropped original images. ,