Therapeutic potential of pentamidine for glioma-initiating cells and glioma cells through multimodal antitumor effects
© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association..
Glioma-initiating cells, which comprise a heterogeneous population of glioblastomas, contribute to resistance against aggressive chemoradiotherapy. Using drug reposition, we investigated a therapeutic drug for glioma-initiating cells. Drug screening was undertaken to select candidate agents that inhibit proliferation of two different glioma-initiating cells lines. The alteration of proliferation and stemness of the two glioma-initiating cell lines, and proliferation, migration, cell cycle, and survival of these two differentiated glioma-initiating cell lines and three different glioblastoma cell lines treated with the candidate agent were evaluated. We also used a xenograft glioma mouse model to evaluate anticancer effects of treated glioma cell lines. Among the 1301 agents, pentamidine-an antibiotic for Pneumocystis jirovecii-emerged as a successful antiglioma agent. Pentamidine treatment suppressed proliferation and stemness in glioma-initiating cell lines. Proliferation and migration were inhibited in all differentiated glioma-initiating cells and glioblastoma cell lines, with cell cycle arrest and caspase-dependent apoptosis induction. The in vivo study reproduced the same findings as the in vitro studies. Pentamidine showed a stronger antiproliferative effect on glioma-initiating cells than on differentiated cells. Western blot analysis revealed pentamidine inhibited phosphorylation of signal transducer and activator of transcription 3 in all cell lines, whereas Akt expression was suppressed in glioma-initiating cells but not in differentiated lines. In the present study, we identified pentamidine as a potential therapeutic drug for glioma. Pentamidine could be promising for the treatment of glioblastomas by targeting both glioma-initiating cells and differentiated cells through its multifaceted antiglioma effects.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2023 |
---|---|
Erschienen: |
2023 |
Enthalten in: |
Zur Gesamtaufnahme - volume:114 |
---|---|
Enthalten in: |
Cancer science - 114(2023), 7 vom: 23. Juli, Seite 2920-2930 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Tamai, Sho [VerfasserIn] |
---|
Links: |
---|
Themen: |
673LC5J4LQ |
---|
Anmerkungen: |
Date Completed 07.07.2023 Date Revised 18.07.2023 published: Print-Electronic Citation Status MEDLINE |
---|
doi: |
10.1111/cas.15827 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM356456781 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM356456781 | ||
003 | DE-627 | ||
005 | 20231226070513.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231226s2023 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1111/cas.15827 |2 doi | |
028 | 5 | 2 | |a pubmed24n1188.xml |
035 | |a (DE-627)NLM356456781 | ||
035 | |a (NLM)37142416 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Tamai, Sho |e verfasserin |4 aut | |
245 | 1 | 0 | |a Therapeutic potential of pentamidine for glioma-initiating cells and glioma cells through multimodal antitumor effects |
264 | 1 | |c 2023 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 07.07.2023 | ||
500 | |a Date Revised 18.07.2023 | ||
500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a © 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. | ||
520 | |a Glioma-initiating cells, which comprise a heterogeneous population of glioblastomas, contribute to resistance against aggressive chemoradiotherapy. Using drug reposition, we investigated a therapeutic drug for glioma-initiating cells. Drug screening was undertaken to select candidate agents that inhibit proliferation of two different glioma-initiating cells lines. The alteration of proliferation and stemness of the two glioma-initiating cell lines, and proliferation, migration, cell cycle, and survival of these two differentiated glioma-initiating cell lines and three different glioblastoma cell lines treated with the candidate agent were evaluated. We also used a xenograft glioma mouse model to evaluate anticancer effects of treated glioma cell lines. Among the 1301 agents, pentamidine-an antibiotic for Pneumocystis jirovecii-emerged as a successful antiglioma agent. Pentamidine treatment suppressed proliferation and stemness in glioma-initiating cell lines. Proliferation and migration were inhibited in all differentiated glioma-initiating cells and glioblastoma cell lines, with cell cycle arrest and caspase-dependent apoptosis induction. The in vivo study reproduced the same findings as the in vitro studies. Pentamidine showed a stronger antiproliferative effect on glioma-initiating cells than on differentiated cells. Western blot analysis revealed pentamidine inhibited phosphorylation of signal transducer and activator of transcription 3 in all cell lines, whereas Akt expression was suppressed in glioma-initiating cells but not in differentiated lines. In the present study, we identified pentamidine as a potential therapeutic drug for glioma. Pentamidine could be promising for the treatment of glioblastomas by targeting both glioma-initiating cells and differentiated cells through its multifaceted antiglioma effects | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a STAT3 | |
650 | 4 | |a drug repositioning | |
650 | 4 | |a glioma | |
650 | 4 | |a glioma-initiating cell | |
650 | 4 | |a pentamidine | |
650 | 7 | |a Pentamidine |2 NLM | |
650 | 7 | |a 673LC5J4LQ |2 NLM | |
700 | 1 | |a Ichinose, Toshiya |e verfasserin |4 aut | |
700 | 1 | |a Jiapaer, Shabierjiang |e verfasserin |4 aut | |
700 | 1 | |a Hirai, Nozomi |e verfasserin |4 aut | |
700 | 1 | |a Sabit, Hemragul |e verfasserin |4 aut | |
700 | 1 | |a Tanaka, Shingo |e verfasserin |4 aut | |
700 | 1 | |a Kinoshita, Masashi |e verfasserin |4 aut | |
700 | 1 | |a Kobayashi, Masahiko |e verfasserin |4 aut | |
700 | 1 | |a Hirao, Atsushi |e verfasserin |4 aut | |
700 | 1 | |a Nakada, Mitsutoshi |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Cancer science |d 2003 |g 114(2023), 7 vom: 23. Juli, Seite 2920-2930 |w (DE-627)NLM12479498X |x 1349-7006 |7 nnns |
773 | 1 | 8 | |g volume:114 |g year:2023 |g number:7 |g day:23 |g month:07 |g pages:2920-2930 |
856 | 4 | 0 | |u http://dx.doi.org/10.1111/cas.15827 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 114 |j 2023 |e 7 |b 23 |c 07 |h 2920-2930 |