Caffeine-Mediated Inhibition of Calcium Release Channel Inositol 1,4,5-Trisphosphate Receptor Subtype 3 Blocks Glioblastoma Invasion and Extends Survival

被引：158

作者：

Kang, Sang Soo ^{[7
]}

Han, Kyung-Seok ^{[1
,6
]}

Ku, Bo Mi ^{[7
]}

Lee, Yeon Kyung ^{[7
]}

Hong, Jinpyo ^{[5
]}

Shin, Hye Young ^{[3
]}

Almonte, Antoine G. ^{[9
]}

Woo, Dong Ho ^{[1
,6
]}

Brat, Daniel J. ^{[9
]}

Hwang, Eun Mi ^{[7
]}

Yoo, Seung Hyun ^{[8
]}

Chung, Chun Kee ^{[3
]}

Park, Sung-Hye ^{[4
]}

Paek, Sun Ha ^{[3
]}

Roh, Eun Joo ^{[2
]}

Lee, Sung Joong ^{[5
]}

Park, Jae-Yong ^{[7
]}

Traynelis, Stephen F. ^{[9
]}

Lee, C. Justin ^{[1
,6
]}

机构：

[1] Korea Inst Sci & Technol, Ctr Neural Sci, Future Fus Technol Lab, Seoul 136791, South Korea

[2] Korea Inst Sci & Technol, Div Life Sci, Seoul 136791, South Korea

[3] Seoul Natl Univ, Coll Med, Canc Res Inst, Clin Res Inst,Dept Neurosurg, Seoul, South Korea

[4] Seoul Natl Univ, Coll Med, Canc Res Inst, Clin Res Inst,Dept Pathol, Seoul, South Korea

[5] Seoul Natl Univ, Sch Dent, Dept Oral Physiol, Program Mol & Cellular Neurosci, Seoul, South Korea

[6] Univ Sci & Technol, Neurosci Program, Taejon, South Korea

[7] Gyeongsang Natl Univ, Sch Med, Inst Hlth Sci, Dept Physiol,Dept Anat & Neurobiol, Jinju, South Korea

[8] Inha Univ, Sch Med, Dept Biochem, Inchon, South Korea

[9] Emory Univ, Dept Pharmacol, Atlanta, GA 30322 USA

来源：

CANCER RESEARCH | 2010年 / 70卷 / 03期

关键词：

GROWTH-FACTOR RECEPTOR; UVB-INDUCED APOPTOSIS; SKH-1; MICE; MIGRATION; SIGNALS; PLASMA; COMMON; BRAIN; CELLS;

D O I：

10.1158/0008-5472.CAN-09-2886

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 (IP(3)R3), the expression of which is increased in glioblastoma cells. Consequently, by inhibiting IP(3)R3-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 IP(3)R3 as a novel therapeutic target and identify caffeine as a possible adjunct therapy to slow invasive growth of glioblastoma. Cancer Res; 70(3); 1173-83. (C)2010 AACR.

引用

页码：1173 / 1183

页数：11

共 23 条

[1] The versatility and universality of calcium signalling [J].