Induction of microRNA-146a is involved in curcumin-mediated enhancement of temozolomide cytotoxicity against human glioblastoma

Abstract

MicroRNA (miR)-146a is a negative regulator of nuclear factor-κB (NF-κB) signaling that affects tumor growth and survival. The present study was undertaken to determine whether the cytotoxicity of curcumin (diferuloylmethane), a natural polyphenolic compound isolated from turmeric (Curcuma longa Linn), in glioblastoma cells is mediated through upregulation of miR.-146a. Human U.-87 MG glioblastoma cells were treated with curcumin and temozolomide (TMZ) alone or in combination, and cell proliferation and apoptosis were assessed. The involvement of miR.-146a and NF.-κB signaling in curcumin.-mediated chemosensitization was explored. Curcumin exposure led to upregulation of miR.-146a in U.-87 MG cells. Combined curcumin and TMZ treatment significantly (P<0.05) inhibited U.-87 MG cell proliferation and induced apoptotic death, compared with each alone. Notably, curcumin.-mediated enhancement of TMZ.-induced apoptosis was blocked by depletion of miR.-146a. By contrast, miR.-146a overexpression enhanced apoptosis and suppressed NF.-κB activation in TMZ.-treated cells. Additionally, pharmacological inhibition of NF.-κB signaling significantly increased TMZ.-induced apoptosis. To the best of our knowledge, the present study provides the first evidence that upregulation of miR.-146a and inactivation of NF.-κB signaling mediates the sensitization of human glioblastoma cells to TMZ-induced apoptosis by curcumin.