title: Demethoxycurcumin was prior to temozolomide on inhibiting proliferation and induced apoptosis of glioblastoma stem cells.
abstract: Temozolomide (TMZ) is widely used for treating glioblastoma (GBM), which can effectively inhibit the GBM growth for some months; however, it still could not prevent the invariable recurrence of GBM. The existence of glioma stem cells (GSCs) was considered to be a key factor. But TMZ has poor effects on GSCs. Recently, demethoxycurcumin (DMC) has been shown to display anti-tumor activities in malignant gliomas. However, its effects and the potential mechanisms on GSCs were still unclear. Our study showed that DMC was prior to TMZ on resulting in a significant increase in GSC apoptosis and a marked inhibition of cell growth in vitro. And combined treatment of DMC and TMZ showed more significant anti-GSC effects. Further research into the underlying mechanism demonstrated that this novel combinatorial regimen leads to changes of multiple cell signaling pathways including reactive oxygen species (ROS) production and caspase-3 signaling mitochondria-related apoptosis activation as well as inactivation of JAK/STAT3 signaling pathway. Taken together, our data demonstrate that the anti-GSC effects of DMC are better than TMZ, and combined treatment of DMC and TMZ has much stronger effects on GSCs.
authors: Department of Neurosurgery, The First People's Hospital of Kunshan Affiliated with Jiangsu University, Suzhou, 215300, People's Republic of China. sl1012002322@126.com.
authors: Lei
authors: L
authors: Shi
authors: Department of Neurosurgery, Suzhou Kowloon Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, Suzhou, 215021, People's Republic of China.
authors: Xifeng
authors: X
authors: Fei
authors: Department of Neurosurgery, Suzhou Kowloon Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, Suzhou, 215021, People's Republic of China. wanyiwzm@126.com.
authors: Zhimin
authors: Z
authors: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D036381:Diarylheptanoids; D005909:Glioblastoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D061251:Primary Cell Culture; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000077204:Temozolomide
chemical_list: D036381:Diarylheptanoids; D017382:Reactive Oxygen Species; D003606:Dacarbazine; D053148:Caspase 3; D003474:Curcumin; C050229:demethoxycurcumin; D000077204:Temozolomide
keywords: Apoptosis; Demethoxycurcumin; Glioblastoma stem cell; Proliferation; Temozolomide