Induction of microRNA-146a is involved in curcumin-mediated enhancement of temozolomide cytotoxicity against human glioblastoma.
Mol Med Rep. 2015 Jul 17. Epub 2015 Jul 17. PMID: 26239619
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 upregulationof 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‑treatedcells. 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.