Caffeine-Mediated Inhibition of Calcium Release Channel Inositol 1,4,5-Trisphosphate Receptor Subtype 3 Blocks Glioblastoma Invasion and Extends Survival
- Caffeine-Mediated Inhibition of Calcium Release Channel Inositol 1,4,5-Trisphosphate Receptor Subtype 3 Blocks Glioblastoma Invasion and Extends Survival
- 강상수; 한경석; 구보미; 이연경; 홍진표; 신혜영; Antoine Almonte; 우동호; Daniel Brat; 황은미; 유승현; 정춘기; 박성혜; 백선하; 노은주; 이성중; 박재용; Stephen Traynelis; 이창준
- Issue Date
- Cancer research
- VOL 70, NO 3, 1173-1183
- Calcium signaling is important in many signaling processes in cancer cell proliferation and motility including
in deadly glioblastomas of the brain that aggressively invade neighboring tissue. We hypothesized that disturbing
Ca2+ signaling pathways might decrease the invasive behavior of giloblastoma, extending survival. Evaluating a
panel of small-molecule modulators of Ca2+ signaling, we identified caffeine as an inhibitor of glioblastoma cell
motility. Caffeine, which is known to activate ryanodine receptors, paradoxically inhibits Ca2+ increase by inositol
1,4,5-trisphospate receptor subtype 3 (IP3R3), the expression of which is increased in glioblastoma cells.
Consequently, by inhibiting IP3R3-mediated Ca2+ release, caffeine inhibited migration of glioblastoma cells in
various in vitro assays. Consistent with these effects, caffeine greatly increased mean survival in a mouse xenograft
model of glioblastoma. These findings suggest IP3R3 as a novel therapeutic target and identify caffeine as a
possible adjunct therapy to slow invasive growth of glioblastoma.
- Appears in Collections:
- KIST Publication > Article
- Files in This Item:
There are no files associated with this item.
- RIS (EndNote)
- XLS (Excel)
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.