Referenced in: none

Automatically associated channels: Slo1

Title: Caffeine-mediated inhibition of calcium release channel inositol 1,4,5-trisphosphate receptor subtype 3 blocks glioblastoma invasion and extends survival.

Authors: Sang Soo Kang, Kyung-Seok Han, Bo Mi Ku, Yeon Kyung Lee, Jinpyo Hong, Hye Young Shin, Antoine G Almonte, Dong Ho Woo, Daniel J Brat, Eun Mi Hwang, Seung Hyun Yoo, Chun Kee Chung, Sung-Hye Park, Sun Ha Paek, Eun Joo Roh, Sung Joong Lee, Jae-Yong Park, Stephen F Traynelis, C Justin Lee

Journal, date & volume: Cancer Res., 2010 Feb 1 , 70, 1173-83

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20103623

Abstract
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 Ca(2+) signaling pathways might decrease the invasive behavior of giloblastoma, extending survival. Evaluating a panel of small-molecule modulators of Ca(2+) signaling, we identified caffeine as an inhibitor of glioblastoma cell motility. Caffeine, which is known to activate ryanodine receptors, paradoxically inhibits Ca(2+) increase by inositol 1,4,5-trisphospate receptor subtype 3 (IP(3)R3), the expression of which is increased in glioblastoma cells. Consequently, by inhibiting IP(3)R3-mediated Ca(2+) 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 IP(3)R3 as a novel therapeutic target and identify caffeine as a possible adjunct therapy to slow invasive growth of glioblastoma.