Eugenol triggers apoptosis in breast cancer cells through E2F1/survivin down-regulation

BMC Cancer

Research Article

Ibtehaj Al-Sharif¹  Abdelilah Aboussekhra¹  Adnane Remmal² 

[1] Department of Molecular Oncology, King Faisal Specialist Hospital and Research Center, PO BOX 3354, MBC # 03-66, 11211, Riyadh, Saudi Arabia;Faculté des Sciences Fès, Laboratoire de Biotechnologie Atlas, Fès, Morocco;

关键词: Apoptosis;    Breast cancer;    Eugenol;    E2F1;    Survivin;   

DOI  :  10.1186/1471-2407-13-600

 received in 2013-07-14, accepted in 2013-11-28,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundBreast cancer is a major health problem that threatens the lives of millions of women worldwide each year. Most of the chemotherapeutic agents that are currently used to treat this complex disease are highly toxic with long-term side effects. Therefore, novel generation of anti-cancer drugs with higher efficiency and specificity are urgently needed.MethodsBreast cancer cell lines were treated with eugenol and cytotoxicity was measured using the WST-1 reagent, while propidium iodide/annexinV associated with flow cytometry was utilized in order to determine the induced cell death pathway. The effect of eugenol on apoptotic and pro-carcinogenic proteins, both in vitro and in tumor xenografts was assessed by immunoblotting. While RT-PCR was used to determine eugenol effect on the E2F1 and survivin mRNA levels. In addition, we tested the effect of eugenol on cell proliferation using the real-time cell electronic sensing system.ResultsEugenol at low dose (2 μM) has specific toxicity against different breast cancer cells. This killing effect was mediated mainly through inducing the internal apoptotic pathway and strong down-regulation of E2F1 and its downstream antiapoptosis target survivin, independently of the status of p53 and ERα. Eugenol inhibited also several other breast cancer related oncogenes, such as NF-κB and cyclin D1. Moreover, eugenol up-regulated the versatile cyclin-dependent kinase inhibitor p21WAF1 protein, and inhibited the proliferation of breast cancer cells in a p53-independent manner. Importantly, these anti-proliferative and pro-apoptotic effects were also observed in vivo in xenografted human breast tumors.ConclusionEugenol exhibits anti-breast cancer properties both in vitro and in vivo, indicating that it could be used to consolidate the adjuvant treatment of breast cancer through targeting the E2F1/survivin pathway, especially for the less responsive triple-negative subtype of the disease.

【 授权许可】

Unknown   
© Al-Sharif et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.