title: Rhus coriaria suppresses angiogenesis, metastasis and tumor growth of breast cancer through inhibition of STAT3, NFκB and nitric oxide pathways.
abstract: Recently, we reported that Rhus coriaria exhibits anticancer activities by promoting cell cycle arrest and autophagic cell death of the metastatic triple negative MDA-MB-231 breast cancer cells. Here, we investigated the effect of Rhus coriaria on the migration, invasion, metastasis and tumor growth of TNBC cells. Our current study revealed that non-cytotoxic concentrations of Rhus coriaria significantly inhibited migration and invasion, blocked adhesion to fibronectin and downregulated MMP-9 and prostaglandin E2 (PgE2). Not only did Rhus coriaria decrease their adhesion to HUVECs and to lung microvascular endothelial (HMVEC-L) cells, but it also inhibited the transendothelial migration of MDA-MB-231 cells through TNF-α-activated HUVECs. Furthermore, we found that Rhus coriaria inhibited angiogenesis, reduced VEGF production in both MDA-MB-231 and HUVECs and downregulated the inflammatory cytokines TNF-α, IL-6 and IL-8. The underlying mechanism for Rhus coriaria effects appears to be through inhibiting NFκB, STAT3 and nitric oxide (NO) pathways. Most importantly, by using chick embryo tumor growth assay, we showed that Rhus coriaria suppressed tumor growth and metastasis in vivo. The results described in the present study identify Rhus coriaria as a promising chemopreventive and therapeutic candidate that modulate triple negative breast cancer growth and metastasis.
authors.affiliation: Department of Biology, College of Science, UAE University, United Arab Emirates University, Al-Ain, P.O. Box 15551, United Arab Emirates.
authors.forename: Hussain
authors.initials: H
authors.lastname: El Hasasna
authors.affiliation: Department of Biological and Environmental Sciences, College of Arts and Sciences, Qatar University, P.O. Box: 2713, Doha, Qatar.
authors.forename: Alaaeldin
authors.initials: A
authors.lastname: Saleh
authors.affiliation: Department of Biology, College of Science, UAE University, United Arab Emirates University, Al-Ain, P.O. Box 15551, United Arab Emirates.
authors.forename: Halima
authors.initials: H
authors.lastname: Al Samri
authors.affiliation: Department of Biology, College of Science, UAE University, United Arab Emirates University, Al-Ain, P.O. Box 15551, United Arab Emirates.
authors.forename: Khawlah
authors.initials: K
authors.lastname: Athamneh
authors.affiliation: Department of Pharmacology &Therapeutics, College of Medicine &Health Sciences, United Arab Emirates University, Al-Ain, P.O. Box: 17666, United Arab Emirates.
authors.forename: Samir
authors.initials: S
authors.lastname: Attoub
authors.affiliation: Department of Pharmacology &Therapeutics, College of Medicine &Health Sciences, United Arab Emirates University, Al-Ain, P.O. Box: 17666, United Arab Emirates.
authors.forename: Kholoud
authors.initials: K
authors.lastname: Arafat
authors.affiliation: Department of Biology, College of Science, UAE University, United Arab Emirates University, Al-Ain, P.O. Box 15551, United Arab Emirates.
authors.forename: Nehla
authors.initials: N
authors.lastname: Benhalilou
authors.affiliation: Department of Biology, College of Science, UAE University, United Arab Emirates University, Al-Ain, P.O. Box 15551, United Arab Emirates.
authors.forename: Sofyan
authors.initials: S
authors.lastname: Alyan
authors.affiliation: INSERM U823, Université Joseph Fourier, BP170, 38042 Grenoble, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Viallet
authors.affiliation: Department of Biology, College of Science, UAE University, United Arab Emirates University, Al-Ain, P.O. Box 15551, United Arab Emirates.
authors.forename: Yusra
authors.initials: Y
authors.lastname: Al Dhaheri
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut, PO Box 11-0236, Lebanon.|Department of Biological and Environmental Sciences, College of Arts and Sciences, Qatar University, PO Box: 2713, Doha, Qatar.
authors.forename: Ali
authors.initials: A
authors.lastname: Eid
authors.affiliation: Department of Biology, College of Science, UAE University, United Arab Emirates University, Al-Ain, P.O. Box 15551, United Arab Emirates.
authors.forename: Rabah
authors.initials: R
authors.lastname: Iratni
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002642:Chick Embryo; D016207:Cytokines / Q000378:metabolism; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D029045:Rhus; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016207:Cytokines; D016328:NF-kappa B; D009363:Neoplasm Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D009569:Nitric Oxide