Morusin Induces TRAIL Sensitization by Regulating EGFR and DR5 in Human Glioblastoma Cells

Dain Park, In Jin Ha, Sang Yoon Park, Minji Choi, Sung Lyul Lim, Sung Hoon Kim, Jun Hee Lee, Kwang Seok Ahn, Miyong Yun, Seok Geun Lee

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)317-323
Number of pages7
JournalJournal of Natural Products
Volume79
Issue number2
DOIs
Publication statusPublished - 26 Feb 2016

Bibliographical note

Publisher Copyright:
© 2016 The American Chemical Society and American Society of Pharmacognosy.

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