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AuthorEl Hasasna, Hussain
AuthorAthamneh, Khawlah
AuthorAl Samri, Halima
AuthorKaruvantevida, Noushad
AuthorAl Dhaheri, Yusra
AuthorHisaindee, Soleiman
AuthorRamadan, Gaber
AuthorAl Tamimi, Nedaa
AuthorAbuQamar, Synan
AuthorEid, Ali
AuthorIratni, Rabah
Available date2016-11-07T10:48:00Z
Publication Date2015-08-12
Publication NameScientific Reportsen_US
Identifierhttp://dx.doi.org/10.1038/srep13013
CitationEl Hasasna H, Athamneh K, Al Samri H, et al. Rhus coriaria induces senescence and autophagic cell death in breast cancer cells through a mechanism involving p38 and ERK1/2 activation. Scientific Reports. 2015;5:13013.
URIhttp://hdl.handle.net/10576/4978
AbstractHere, we investigated the anticancer effect of Rhus coriaria on three breast cancer cell lines. We demonstrated that Rhus coriaria ethanolic extract (RCE) inhibits the proliferation of these cell lines in a time- and concentration-dependent manner. RCE induced senescence and cell cycle arrest at G1 phase. These changes were concomitant with upregulation of p21, downregulation of cyclin D1, p27, PCNA, c-myc, phospho-RB and expression of senescence-associated β-galactosidase activity. No proliferative recovery was detected after RCE removal. Annexin V staining and PARP cleavage analysis revealed a minimal induction of apoptosis in MDA-MB-231 cells. Electron microscopy revealed the presence of autophagic vacuoles in RCE-treated cells. Interestingly, blocking autophagy by 3-methyladenine (3-MA) or chloroquine (CQ) reduced RCE-induced cell death and senescence. RCE was also found to activate p38 and ERK1/2 signaling pathways which coincided with induction of autophagy. Furthermore, we found that while both autophagy inhibitors abolished p38 phosphorylation, only CQ led to significant decrease in pERK1/2. Finally, RCE induced DNA damage and reduced mutant p53, two events that preceded autophagy. Our findings provide strong evidence that R. coriaria possesses strong anti-breast cancer activity through induction of senescence and autophagic cell death, making it a promising alternative or adjunct therapeutic candidate against breast cancer.
SponsorUAEU Program for Advanced Research (Grant 31S111-UPAR) and by the Zayed Center for Health Sciences (ZCHS) research grant (grant 31R021) and College of Science Individual Research Grant (grant 31S123) to Rabah Iratni.
Languageen
PublisherNature Publishing Group
SubjectPreclinical research
SubjectBreast cancer
Subjectcancer treatment
TitleRhus coriaria induces senescence and autophagic cell death in breast cancer cells through a mechanism involving p38 and ERK1/2 activation
TypeArticle
Volume Number5
dc.identifier.essn 2045-2322


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