title: Morusin Induces TRAIL Sensitization by Regulating EGFR and DR5 in Human Glioblastoma Cells.
abstract: Glioblastoma is one of the most malignant primary tumors, and the prognosis for glioblastoma patients remains poor. Tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL) is considered a promising anticancer agent due to its remarkable ability to selectively kill tumor cells. However, since many cancers are resistant to TRAIL, strategies to overcome resistance are required for the successful use of TRAIL in the clinic. In the present study, the potential of morusin as a TRAIL sensitizer in human glioblastoma cells was evaluated. Treatment with TRAIL or morusin alone showed weak cytotoxicity in human glioblastoma cells. However, combination treatment of TRAIL with morusin synergistically decreased cell viability and increased apoptosis compared with single treatment. Morusin induced expression of death receptor 5 (DR5), but not DR4 or decoy receptors (DcR1 and DcR2). Furthermore, morusin significantly decreased anti-apoptotic molecules survivin and XIAP. In addition, morusin reduced expression of EGFR and PDFGR as well as phosphorylation of STAT3, possibly mediating down-regulation of survivin and XIAP. Together these results suggest that morusin enhances TRAIL sensitivity in human glioblastoma cells through regulating expression of DR5 and EGFR. Therefore, the combination treatment of TRAIL and morusin may be a new therapeutic strategy for malignant glioma patients.
authors.forename: Dain
authors.initials: D
authors.lastname: Park
authors.affiliation: Korean Medicine Clinical Trial Center, Kyung Hee University Korean Medicine Hospital , Seoul 02447, Republic of Korea.
authors.forename: In Jin
authors.initials: IJ
authors.lastname: Ha
authors.forename: Sang-Yoon
authors.initials: SY
authors.lastname: Park
authors.forename: Minji
authors.initials: M
authors.lastname: Choi
authors.forename: Sung-Lyul
authors.initials: SL
authors.lastname: Lim
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Korean Medicine Clinical Trial Center, Kyung Hee University Korean Medicine Hospital , Seoul 02447, Republic of Korea.
authors.forename: Jun-Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: Kwang Seok
authors.initials: KS
authors.lastname: Ahn
authors.affiliation: Korean Medicine Clinical Trial Center, Kyung Hee University Korean Medicine Hospital , Seoul 02447, Republic of Korea.
authors.forename: Miyong
authors.initials: M
authors.lastname: Yun
authors.affiliation: Korean Medicine Clinical Trial Center, Kyung Hee University Korean Medicine Hospital , Seoul 02447, Republic of Korea.
authors.forename: Seok-Geun
authors.initials: SG
authors.lastname: Lee
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism*; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D005909:Glioblastoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D015394:Molecular Structure; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000187:drug effects / Q000235:genetics*; D050796:STAT3 Transcription Factor / Q000187:drug effects; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism
chemical_list: D005419:Flavonoids; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D050796:STAT3 Transcription Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C057451:morusin; D066246:ErbB Receptors