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Identification of acetylshikonin as a novel tubulin polymerization inhibitor with antitumor activity in human hepatocellular carcinoma cells.
Hu, Siming; Li, Yongchuan; Zhou, Junqiu; Xu, Kun; Pang, Yanqing; Weiskirchen, Ralf; Ocker, Matthias; Ouyang, Fen.
Afiliación
  • Hu S; Department of Laboratory Medicine, Nanfang Hospital Taihe Branch, Guangzhou, China.
  • Li Y; First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China.
  • Zhou J; Department of Laboratory Medicine, Nanfang Hospital Baiyun Branch, Southern Medical University, Guangzhou, China.
  • Xu K; Department of Laboratory Medicine, Nanfang Hospital Baiyun Branch, Southern Medical University, Guangzhou, China.
  • Pang Y; Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China.
  • Weiskirchen R; Institute of Molecular Pathobiochemistry, Experimental Gene Therapy, and Clinical Chemistry (IFMPEGKC), RWTH University Hospital Aachen, Aachen, Germany.
  • Ocker M; Medical Department, Division of Hematology, Oncology, and Cancer Immunology Campus Charité Mitte, Charité University Medicine Berlin, Berlin, Germany.
  • Ouyang F; Department of Laboratory Medicine, Nanfang Hospital Baiyun Branch, Southern Medical University, Guangzhou, China.
J Gastrointest Oncol ; 14(6): 2574-2586, 2023 Dec 31.
Article en En | MEDLINE | ID: mdl-38196542
ABSTRACT

Background:

Microtubules are attractive targets for anticancer drugs. However, the microtubule-targeting agents (MTAs) currently in clinical use exhibit inevitable drug resistance. Therefore, there is an urgent need to discover novel MTAs for the clinical treatment of cancer.

Methods:

Bioactive compounds extracted from Lithospermum erythrorhizon were assessed for in vitro anti-proliferative activities against a panel of human cancer cell lines using cell counting kit-8 (CCK-8) assay. Tubulin polymerization inhibition assay, colchicine competitive binding site assay, and immunofluorescence were used to validate the tubulin inhibition effect of acetylshikonin. Flow cytometry, Hoechst staining, and caspase-3 activity evaluation were performed to assess cell cycle arrest and cell apoptosis. 5,5',6,6'-tetrachloro-1,1',3,3'-tetramethylbenzimidazolylcarbocyanine iodide (JC-1) staining and dichloro-dihydro-fluorescein diacetate (DCFH-DA) staining were used to evaluate mitochondrial membrane potential (MMP) and reactive oxygen species (ROS), respectively.

Results:

Acetylshikonin exhibited potent anti-proliferative activities against a panel of human cancer cell lines (IC50 values 1.09-7.26 µM) and displayed comparable cytotoxicity against several drug-resistant cell lines. Further mechanism studies revealed that acetylshikonin induced cell cycle arrest of MHCC-97H cells at G2/M phase, and significantly promoted apoptosis marked by a collapse of MMP and abnormal ROS accumulation.

Conclusions:

In this study, acetylshikonin was identified as MTA against hepatocellular carcinoma and can serve as a promising lead compound for further development of anti-cancer drug, underscoring its potential clinical significance.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Diagnostic_studies Idioma: En Revista: J Gastrointest Oncol Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: China
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Diagnostic_studies Idioma: En Revista: J Gastrointest Oncol Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: China