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Effects of Lomerizine and Its Metabolite on Glioblastoma Cells.
Uemichi, Yuki; Mabuchi, Miyuki; Tsuchiya, Natsumi; Yasuda, Seina; Nakao, Shuhei; Shimizu, Tadashi.
Afiliación
  • Uemichi Y; School of Pharmacy, Hyogo Medical University, Kobe, Japan.
  • Mabuchi M; School of Pharmacy, Hyogo Medical University, Kobe, Japan my-mabuchi@hyo-med.ac.jp.
  • Tsuchiya N; School of Pharmacy, Hyogo Medical University, Kobe, Japan.
  • Yasuda S; School of Pharmacy, Hyogo Medical University, Kobe, Japan.
  • Nakao S; School of Pharmacy, Hyogo Medical University, Kobe, Japan.
  • Shimizu T; School of Pharmacy, Hyogo Medical University, Kobe, Japan.
Anticancer Res ; 44(7): 2943-2952, 2024 Jul.
Article en En | MEDLINE | ID: mdl-38925834
ABSTRACT
BACKGROUND/

AIM:

Glioblastoma is an incurable cancer with limited treatment options and a low survival rate. Temozolomide is the standard marketed small-molecule agent for glioblastoma therapy; therefore, we aimed to find new drugs among the marketed medicines for brain diseases because of their cerebral migratory property and found lomerizine, used for the treatment of migraine. MATERIALS AND

METHODS:

We evaluated the effect of lomerizine and its metabolites against U251 glioblastoma cells and temozolomide-resistant cells, T98G and GB-1, caused by the expression of O(6)-methylguanine-DNA methyltransferase or P-glycoprotein, compared with temozolomide, and combined with it. The mechanism of action was investigated using inhibitors of necrosis or apoptosis.

RESULTS:

Lomerizine and its metabolite (M6) inhibited the proliferation of glioblastoma cells with greater potency and efficacy than temozolomide, including against temozolomide-resistant cells. The effects of lomerizine and M6 on glioblastoma were mainly attributed to the inhibition of proliferation because cells were not rescued by cell death inhibitors, such as necrosis or apoptosis inhibitors, although they were slightly rescued by necrostatin-1. Additionally, lomerizine and M6 combined with temozolomide were more effective at inhibiting the proliferation of U251 and GB-1 cells at some doses than single treatments.

CONCLUSION:

Lomerizine has been used for migraine treatment because of its brain-penetrating properties without serious side-effects; thus, it might potentially be expected to be used alone for glioblastoma, including temozolomide-resistant glioblastoma, or in combination with temozolomide.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Apoptosis / Glioblastoma / Proliferación Celular / Temozolomida Límite: Humans Idioma: En Revista: Anticancer Res Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Grecia
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Apoptosis / Glioblastoma / Proliferación Celular / Temozolomida Límite: Humans Idioma: En Revista: Anticancer Res Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Grecia