期刊
JOURNAL OF CELLULAR PHYSIOLOGY
卷 234, 期 4, 页码 3147-3157出版社
WILEY
DOI: 10.1002/jcp.27309
关键词
17 beta-estradiol; estrogen receptor a; human breast cancer cells; neuroglobin; paclitaxel; resveratrol; signal transduction pathway
资金
- Associazione Italiana per la Ricerca sul Cancro [15221]
Neuroglobin (NGB), an antiapoptotic protein upregulated by 17-estradiol (E2), is part of E2/estrogen receptor (ER) pathway pointed to preserve cancer cell survival in presence of microenvironmental stressors including chemotherapeutic drugs. Here, the possibility that resveratrol (Res), an anticancer plant polyphenol, could increase the susceptibility of breast cancer cells to paclitaxel (Pacl) by affecting E2/ER/NGB pathway has been evaluated. In MCF-7 and T47D (ER-positive), but not in MDA-MB 231 (ER-negative) nor in SK-N-BE (ER and ER positive), Res decreases NGB levels interfering with E2/ER-induced NGB upregulation and with E2-induced ER and protein kinase B phosphorylation. Although Res treatment does not reduce cell viability by itself, this compound potentiates Pacl proapoptotic effects. Notably, the increase of NGB levels by NGB expression vector transfection prevents Pacl or Res/Pacl effects. Taken together, these findings indicate a new Res-based mechanism that acts on tumor cells impairing the E2/ER/NGB signaling pathways and increasing cancer cell susceptibility to chemotherapeutic agent.
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