El Hasasna Hussain, Saleh Alaaeldin, Al Samri Halima, Athamneh Khawlah, Attoub Samir, Arafat Kholoud, Benhalilou Nehla, Alyan Sofyan, Viallet Jean, Al Dhaheri Yusra, Eid Ali, Iratni Rabah
Department of Biology, College of Science, UAE University, United Arab Emirates University, Al-Ain, P.O. Box 15551, United Arab Emirates.
Department of Biological and Environmental Sciences, College of Arts and Sciences, Qatar University, P.O. Box: 2713, Doha, Qatar.
Sci Rep. 2016 Feb 18;6:21144. doi: 10.1038/srep21144.
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.
最近,我们报道了盐肤木通过促进转移性三阴性MDA-MB-231乳腺癌细胞的细胞周期阻滞和自噬性细胞死亡而表现出抗癌活性。在此,我们研究了盐肤木对三阴性乳腺癌(TNBC)细胞迁移、侵袭、转移和肿瘤生长的影响。我们目前的研究表明,盐肤木的非细胞毒性浓度显著抑制迁移和侵袭,阻断与纤连蛋白的黏附,并下调基质金属蛋白酶-9(MMP-9)和前列腺素E2(PgE2)。盐肤木不仅降低了它们与人类脐静脉内皮细胞(HUVECs)和肺微血管内皮(HMVEC-L)细胞的黏附,还抑制了MDA-MB-231细胞通过肿瘤坏死因子-α(TNF-α)激活的HUVECs的跨内皮迁移。此外,我们发现盐肤木抑制血管生成,减少MDA-MB-231细胞和HUVECs中血管内皮生长因子(VEGF)的产生,并下调炎性细胞因子TNF-α、白细胞介素-6(IL-6)和白细胞介素-8(IL-8)。盐肤木发挥作用的潜在机制似乎是通过抑制核因子κB(NFκB)、信号转导和转录激活因子3(STAT3)和一氧化氮(NO)途径。最重要的是,通过使用鸡胚肿瘤生长试验,我们表明盐肤木在体内抑制肿瘤生长和转移。本研究中描述的结果确定盐肤木是一种有前景的化学预防和治疗候选物,可调节三阴性乳腺癌的生长和转移。