title: 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.
authors.affiliation: Department of Neurosurgery, Xiangya 3rd Hospital, Changsha, Hunan 410013, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, Xiangya 3rd Hospital, Changsha, Hunan 410013, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Xiangya 3rd Hospital, Changsha, Hunan 410013, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Cai
authors.affiliation: Hemodialysis Room, Xiangya 3rd Hospital, Changsha, Hunan 410013, P.R. China.
authors.forename: Yu-Dan
authors.initials: YD
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Xiangya 3rd Hospital, Changsha, Hunan 410013, P.R. China.
authors.forename: Zhi-Fei
authors.initials: ZF
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000077204:Temozolomide
chemical_list: D000970:Antineoplastic Agents; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D003606:Dacarbazine; D003474:Curcumin; D000077204:Temozolomide