Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Lohberger, B; Glänzer, D; Kaltenegger, H; Eck, N; Leithner, A; Bauer, R; Kretschmer, N; Steinecker-Frohnwieser, B.
Shikonin derivatives cause apoptosis and cell cycle arrest in human chondrosarcoma cells via death receptors and MAPK regulation.
BMC Cancer. 2022; 22(1):758
Doi: 10.1186/s12885-022-09857-x
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Führende Autor*innen der Med Uni Graz
- Lohberger Birgit
- Co-Autor*innen der Med Uni Graz
- Eck Nicole
- Glänzer Dietmar
- Kaltenegger Heike
- Kretschmer Nadine
- Leithner Andreas
- Steinecker-Frohnwieser Bibiane
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- BACKGROUND: Although chondrosarcoma is the second most common primary malignant bone tumor, treatment options are limited due to its extensive resistance to a chemo- and radiation therapy. Since shikonin has shown potent anticancer activity in various types of cancer cells, it represents a promising compound for the development of a new therapeutic approach. METHODS: The dose-relationships of shikonin and its derivatives acetylshikonin and cyclopropylshikonin on two human chondrosarcoma cell lines were measured using the CellTiter-Glo®. The changes in the cell cycle were presented by flow cytometry. Protein phosphorylation and expression apoptotic markers, MAPKs and their downstream targets were analyzed using western blotting and gene expression were evaluated using RT-qPCR. RESULTS: Chondrosarcoma cells showed a dose-dependent inhibition of cell viability after treatment with shikonin and its derivatives, with the strongest effect for shikonin and IC50 values of 1.3 ± 0.2 µM. Flow cytometric measurements revealed a G2/M arrest of the cells after treatment. Protein and gene expression analysis demonstrated a dose-dependent downregulation of survivin and XIAP, and an upregulation of Noxa, γH2AX, cleaved caspase-8, -9, -3, and -PARP. Furthermore, the expression of various death receptors was modulated. As MAPK signaling pathways play a key role in tumor biology, their phosphorylation pattern and their corresponding downstream gene regulation were analyzed. Treatment with shikonin derivatives caused an inhibition of pSTAT3 and an increase of pAKT and the MAPKs pERK, pJNK, and pp38 in a dose-dependent manner. CONCLUSIONS: These data demonstrated the significant anti-tumorigenic effect of shikonin derivatives in chondrosarcoma and encourage further research.
- Find related publications in this database (using NLM MeSH Indexing)
- Apoptosis - drug effects
- Bone Neoplasms - drug therapy, metabolism, pathology
- Cell Cycle Checkpoints - drug effects
- Cell Line, Tumor - administration & dosage
- Chondrosarcoma - drug therapy, metabolism, pathology
- Humans - administration & dosage
- Mitogen-Activated Protein Kinases - administration & dosage
- Naphthoquinones - pharmacology
- Receptors, Death Domain - metabolism
- Find related publications in this database (Keywords)
- Chondrosarcoma
- Shikonin
- Acetylshikonin
- Cyclopropylshikonin
- Apoptosis
- Death receptors
- MAPK signaling