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

Wu,Hao; Liu,Qiang; Cai,Tao; Chen,Yu‑Dan; Wang,Zhi‑Fei

doi:10.3892/mmr.2015.4087

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

Authors:
- Hao Wu
- Qiang Liu
- Tao Cai
- Yu‑Dan Chen
- Zhi‑Fei Wang
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Affiliations: Department of Neurosurgery, Xiangya 3rd Hospital, Changsha, Hunan 410013, P.R. China, Hemodialysis Room, Xiangya 3rd Hospital, Changsha, Hunan 410013, P.R. China
Published online on: July 17, 2015 https://doi.org/10.3892/mmr.2015.4087
Pages: 5461-5466

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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.

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