Premium
Potentiation of paclitaxel effect by resveratrol in human breast cancer cells by counteracting the 17β‐estradiol/estrogen receptor α/neuroglobin pathway
Author(s) -
Cipolletti Manuela,
Montalesi Emiliano,
Nuzzo Maria Teresa,
Fiocchetti Marco,
Ascenzi Paolo,
Marino Maria
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.27309
Subject(s) - estrogen receptor , resveratrol , downregulation and upregulation , neuroglobin , cancer research , chemistry , viability assay , cancer cell , transfection , estrogen receptor alpha , cell , cancer , pharmacology , microbiology and biotechnology , biology , breast cancer , biochemistry , genetics , globin , gene
Neuroglobin (NGB), an antiapoptotic protein upregulated by 17β‐estradiol (E2), is part of E2/estrogen receptor α (ERα) 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/ERα/NGB pathway has been evaluated. In MCF‐7 and T47D (ERα‐positive), but not in MDA‐MB 231 (ERα‐negative) nor in SK‐N‐BE (ERα and ERβ positive), Res decreases NGB levels interfering with E2/ERα‐induced NGB upregulation and with E2‐induced ERα 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/ERα/NGB signaling pathways and increasing cancer cell susceptibility to chemotherapeutic agent.