American Association for Cancer Research
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Supplementary Figures 1-4. Supplementary Table 1 from Trifluoperazine, a Well-Known Antipsychotic, Inhibits Glioblastoma Invasion by Binding to Calmodulin and Disinhibiting Calcium Release Channel IP3R

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posted on 2023-04-03, 15:48 authored by Seokmin Kang, Jinpyo Hong, Jung Moo Lee, Hyo Eun Moon, Borami Jeon, Jungil Choi, Nal Ae Yoon, Sun Ha Paek, Eun Joo Roh, C. Justin Lee, Sang Soo Kang

Supplementary Figure S1. TFP induces morphological change of U87MG cells, and cell death; Supplementary Figure S2. Body weight is not changed during TFP injection in in vivo glioblastoma skin xenograft model; Supplementary Figure S3. IP3R1, 2 and 3 shRNA knockdown test by western blot and functional knockdown test using GBL 28 primary glioblastoma cells; Supplementary Figure S4. TFP reduces cell viability of several GBL cells;Supplementary Table S1. IP3R 1, 2, 3 and CaM shRNA sequences

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NRF

MEST

Korean National Research Foundation

KU-KIST Graduate School of Science and Technology

National Research Council of Science & Technology

Ministry of Trade, Industry and Energy

MSIP

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ARTICLE ABSTRACT

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 glioblastoma 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. Mol Cancer Ther; 16(1); 217–27. ©2016 AACR.

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