title: Low-Dose DMC Significantly Enhances the Effect of TMZ on Glioma Cells by Targeting Multiple Signaling Pathways Both In Vivo and In Vitro.
abstract: Temozolomide (TMZ) is widely used for treating glioblastoma (GBM), which can effectively inhibit the GBM growth for some months; however, it still cannot prevent the invariable recurrence of GBM. Improving the chemotherapeutic sensitization becomes an urgent agenda. In this study, we found low-dose demethoxycurcumin (DMC) could enhance the sensitivity of TMZ on glioma cells, and high-dose DMC has more significant effects on GBM cells compared with TMZ treatment alone both in vitro and in vivo. And co-administration of DMC and TMZ resulted in a significant increase in GBM apoptosis and a marked inhibition of cell growth pathogenesis of GBM. Mechanistically, DMC and TMZ synergistically increase intracellular level of reactive oxygen species (ROS) production, activate caspase-3-dependent apoptotic pathway, and inactivate of JAK/STAT3 signaling pathway in GBMs, which account for the cell apoptosis and proliferation inhibition. Together, these data implicate that low-dose DMC combined with TMZ represents an effective therapy regimen against GBMs by targeting multiple signaling pathways.
authors.affiliation: Department of Neurosurgery, The First People's Hospital of Kunshan Affiliated with Jiangsu University, Suzhou, 215300, People's Republic of China. shileigff@126.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Neurosurgery, Fourth Affiliated Yancheng Hospital of Nantong University, Yancheng, 224000, People's Republic of China.
authors.forename: Guan
authors.initials: G
authors.lastname: Sun
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D003474:Curcumin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D036381:Diarylheptanoids; D004357:Drug Synergism; D016193:G1 Phase / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D053612:Janus Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*; D000077204:Temozolomide; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D036381:Diarylheptanoids; D009363:Neoplasm Proteins; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D003606:Dacarbazine; D053612:Janus Kinases; D003474:Curcumin; C050229:demethoxycurcumin; D000077204:Temozolomide
keywords: Apoptosis; Demethoxycurcumin; Glioblastoma; Proliferation; Temozolomide