Shikonin inhibits prostate cancer cells metastasis by reducing matrix metalloproteinase-2/-9 expression via AKT/mTOR and ROS/ERK1/2 pathways
| Autor: | Fu-Xing Chen, Yongqiang Chen, Xiliang Cao, Jun-Quan Liu, Lu Zheng, Zhong-Hai Zhou, Xiao-Ting Lv |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
MAPK/ERK pathway
G2 Phase Male Cell cycle checkpoint MAP Kinase Signaling System Immunology Cell Biology p38 Mitogen-Activated Protein Kinases DU145 Cell Movement Cell Line Tumor medicine Immunology and Allergy Humans Neoplasm Metastasis Phosphorylation Protein kinase B PI3K/AKT/mTOR pathway Cell Proliferation Pharmacology Cell growth TOR Serine-Threonine Kinases JNK Mitogen-Activated Protein Kinases Prostatic Neoplasms Cell Cycle Checkpoints Cell cycle Gene Expression Regulation Neoplastic medicine.anatomical_structure Biochemistry Matrix Metalloproteinase 9 Cancer research Matrix Metalloproteinase 2 Reactive Oxygen Species Proto-Oncogene Proteins c-akt Naphthoquinones Signal Transduction |
| Zdroj: | International immunopharmacology. 21(2) |
| ISSN: | 1878-1705 |
| Popis: | Metastasis is one of the most important factors related to prostate cancer therapeutic efficacy. In previous studies, shikonin, an active naphthoquinone isolated from the Chinese medicine Zi Cao, has various anticancer activities both in vivo and in vitro. However, the mechanisms underlying shikonin's anticancer activity are not fully elucidated on prostate cancer cells. In the present study, we aimed to investigate the potential effects of shikonin on prostate cancer cells and the underlying mechanisms by which shikonin exerted its actions. With cell proliferation, flow cytometric cell cycle, migration and invasion assays, we found that shikonin potently suppressed PC-3 and DU145 cell growth by cell cycle arrest at the G2 phase and metastasis in a dose-dependent manner. Mechanically, we presented that shikonin could suppress the metastasis of PC-3 and DU145 cells via inhibiting the matrix metalloproteinase-2 (MMP-2) and MMP-9 expression and activation. In addition, shikonin significantly decreased the phosphorylation of AKT and mTOR in a dose-dependent manner while it induced extracellular signal-regulated kinase (ERK), p38 mitogen activated protein kinase (MAPK) and c-Jun N terminal kinase (JNK) phosphorylation. Further investigation of the underlying mechanism revealed that shikonin also induced the production of reactive oxygen species (ROS) that was reversed by the ROS scavenger dithiothreitol (DTT). Additionally, DTT reversed the shikonin induced activation of ERK1/2, thereby maintaining MMP-2 and MMP-9 expression and restoring cell metastasis. Together, shikonin inhibits aggressive prostate cancer cell migration and invasion by reducing MMP-2/-9 expression via AKT/mTOR and ROS/ERK1/2 pathways and presents a potential novel alternative agent for the treatment of human prostate cancer. |
| Databáze: | OpenAIRE |
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