Tubeimoside-I, an inhibitor of HSPD1, enhances cytotoxicity of oxaliplatin by activating ER stress and MAPK signaling pathways in colorectal cancer.
J Ethnopharmacol
; 336: 118754, 2025 Jan 10.
Article
em En
| MEDLINE
| ID: mdl-39208999
ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE Tubeimoside-I (TBM) promotes various cancer cell death by increasing the reactive oxygen species (ROS) production. However, the specific molecular mechanisms of TBM and its impact on oxaliplatin-mediated anti-CRC activity are not yet fully understood. AIM OF THE STUDY To elucidate the therapeutic effect and underlying molecular mechanism of TBM on oxaliplatin-mediated anti-CRC activity. MATERIALS AND METHODS:
3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, wound healing assays and flow cytometry were conducted to investigate the changes in cell phenotypes and ROS generation. Real-time quantitative PCR (qRT-PCR) and western blotting were performed to detect the expressions of related mRNA and proteins. Finally, mouse xenograft models demonstrated that synergistic anti-tumor effects of combined treatment with TBM and oxaliplatin.RESULTS:
The synergistic enhancement of the anti-tumor effects of oxaliplatin in colon cancer cells by TBM involved in the regulation of ROS-mediated endoplasmic reticulum (ER) stress, C-jun-amino-terminal kinase (JNK), and p38 MAPK signaling pathways. Mechanistically, TBM increased ROS generation in colon cancer cells by inhibiting heat shock protein 60 (HSPD1) expression. Knocking down HSPD1 increased TBM-induced antitumor activity and ROS generation in colon cancer cells. The mouse xenograft tumor models further validated that the combination therapy exhibited stronger anti-tumor effects than monotherapy alone.CONCLUSIONS:
Combined therapy with TBM and oxaliplatin might be an effective therapeutic strategy for some CRC patients.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Saponinas
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Triterpenos
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Neoplasias Colorretais
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Espécies Reativas de Oxigênio
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Sinergismo Farmacológico
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Estresse do Retículo Endoplasmático
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Oxaliplatina
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
J Ethnopharmacol
Ano de publicação:
2025
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
Irlanda