Kang, Seokmin Hong, Jinpyo Lee, Jung Moo Moon, Hyo Eun Jeon, Borami Choi, Jungil Yoon, Nal Ae Paek, Sun Ha Roh, Eun Joo Lee, C. Justin Kang, Sang Soo 2024-01-20T02:32:59Z 2024-01-20T02:32:59Z 2021-09-04 2017-01 1535-7163 https://pubs.kist.re.kr/handle/201004/123281 Calcium (Ca2+) signaling is an important signaling process, implicated in cancer cell proliferation and motility of the deadly glioblastomas that aggressively invade neighboring brain tissue. We have previously demonstrated that caffeine blocks glioblastoma invasion and extends survival by inhibiting Ca2+ release channel inositol 1,4,5-trisphosphate receptor (IP3R) subtype 3. Trifluoperazine (TFP) is an FDA-approved antipsychotic drug for schizophrenia. Interestingly, TFP has been recently reported to show a strong anticancer effect on lung cancer, hepatocellular carcinoma, and T-cell lymphoma. However, the possible anticancer effect of TFP on glioblastoma has not been tested. Here, we report that TFP potently suppresses proliferation, motility, and invasion of glioblas-toma cells in vitro, and tumor growth in in vivo xenograft mouse model. Unlike caffeine, TFP triggers massive and irreversible release of Ca2+ from intracellular stores by IP3R subtype 1 and 2 by directly interacting at the TFP-binding site of a Ca2+-binding protein, calmodulin subtype 2 (CaM2). TFP binding to CaM2 causes a dissociation of CaM2 from IP3R and subsequent opening of IP3R. Compared with the control neural stem cells, various glioblastoma cell lines showed enhanced expression of CaM2 and thus enhanced sensitivity to TFP. On the basis of these findings, we propose TFP as a potential therapeutic drug for glioblastoma by aberrantly and irreversibly increasing Ca2+ in glioblastoma cells. (C) 2016 AACR. English AMER ASSOC CANCER RESEARCH ADJUVANT TEMOZOLOMIDE GROWTH-INHIBITION CELL-CYCLE CANCER SURVIVAL DRUGS RADIOTHERAPY CONCOMITANT RESISTANCE INDUCTION Trifluoperazine, a Well-Known Antipsychotic, Inhibits Glioblastoma Invasion by Binding to Calmodulin and Disinhibiting Calcium Release Channel IP3R Article 10.1158/1535-7163.MCT-16-0169-T 1 MOLECULAR CANCER THERAPEUTICS, v.16, no.1, pp.217 - 227 MOLECULAR CANCER THERAPEUTICS 16 1 217 227 scie scopus 000393695500020 2-s2.0-85010029696 Oncology Oncology Article ADJUVANT TEMOZOLOMIDE GROWTH-INHIBITION CELL-CYCLE CANCER SURVIVAL DRUGS RADIOTHERAPY CONCOMITANT RESISTANCE INDUCTION Trifluoperazine IP3 receptor calcium glioblastoma antipsychotic