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Tubeimoside-I, an inhibitor of HSPD1, enhances cytotoxicity of oxaliplatin by activating ER stress and MAPK signaling pathways in colorectal cancer.
Wu, Tao; Yu, Yun; Tu, Xinyue; Ye, Lihua; Wang, Jiaying; Xie, Chenjun; Kuang, Keke; Yu, Ying; Zhuge, Weishan; Wang, Zhonglin; Cui, Ri; Zheng, Yihu.
Afiliación
  • Wu T; Department of General Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China; Cancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
  • Yu Y; Cancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
  • Tu X; Cancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
  • Ye L; Cancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
  • Wang J; Cancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
  • Xie C; Cancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
  • Kuang K; Cancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
  • Yu Y; Cancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
  • Zhuge W; Cancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
  • Wang Z; The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325003, China.
  • Cui R; Cancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China. Electronic address: wzmucuiri@163.com.
  • Zheng Y; Department of General Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China; Cancer and Anticancer Drug Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China. Electronic address: zhengyihu@fox
J Ethnopharmacol ; 336: 118754, 2025 Jan 10.
Article en 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Saponinas / Triterpenos / Neoplasias Colorrectales / Especies Reactivas de Oxígeno / Sinergismo Farmacológico / Estrés del Retículo Endoplásmico / Oxaliplatino Límite: Animals / Humans / Male Idioma: En Revista: J Ethnopharmacol Año: 2025 Tipo del documento: Article País de afiliación: China Pais de publicación: Irlanda
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Saponinas / Triterpenos / Neoplasias Colorrectales / Especies Reactivas de Oxígeno / Sinergismo Farmacológico / Estrés del Retículo Endoplásmico / Oxaliplatino Límite: Animals / Humans / Male Idioma: En Revista: J Ethnopharmacol Año: 2025 Tipo del documento: Article País de afiliación: China Pais de publicación: Irlanda