Denbinobin, a phenanthrene from Dendrobium nobile, impairs prostate cancer migration by inhibiting Rac1 activity.

Abstract

Prostate cancer is the most prevalent type of cancer in the United States. The most common site of prostate cancer metastasis is bone. CXCL12 is preferentially expressed in bone and is targeted by prostate cancer cells, which over-express the receptor for CXCL12, CXCR4. In response to CXCL12 stimulation, Rac1, a GTPase, along with its effectors, regulates actin polymerization to form lamellipodia, which is a critical event for cell migration. Cortactin, an actin-binding protein, is recruited to the lamellipodia and is phosphorylated at tyrosine residues. The phosphorylated cortactin is also involved in cell migration. The inhibition of Rac1 activity using a dominant negative Rac1 impairs lamellipodial protrusion as well as cortactin translocation and cortactin phosphorylation. Denbinobin, a substance extracted from Dendrobium nobile, has anticancer effects in many cancer cell lines. Whether denbinobin can inhibit prostate cancer cell migration is not clear. Here, we report that denbinobin inhibited Rac1 activity. The inhibition of Rac1 activity prevented lamellipodial formation. Cortactin phosphorylation and translocation to the lamellipodia were also impaired, and PC3 cells were unable to migrate. These results indicate that denbinobin prevents CXCL12-induced PC3 cell migration by inhibiting Rac1 activity.

• Authors: Te-Ling Lu, Chien-Kuo Han, Yuan-Shiun Chang, Te-Jung Lu, Hui-Chi Huang, Bo-Ying Bao, Hsing-Yu Wu, Chieh-Hung Huang, Chia-Yen Li, Tian-Shung Wu
• Journal: The American journal of Chinese medicine (Am J Chin Med) Vol. 42 Issue 6 Pg. 1539-54 ( 2014) ISSN: 1793-6853 [Electronic] Singapore
• PMID: 25427623 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Actins
• Anthraquinones
• Antineoplastic Agents, Phytogenic
• CXCL12 protein, human
• Chemokine CXCL12
• Cortactin
• Phenanthrenes
• RAC1 protein, human
• denbinobin
• rac1 GTP-Binding Protein

Topics

• Actins (metabolism)
• Anthraquinones (pharmacology, therapeutic use)
• Antineoplastic Agents, Phytogenic
• Cell Movement (drug effects)
• Chemokine CXCL12 (physiology)
• Cortactin (metabolism)
• Dendrobium (chemistry)
• Humans
• Male
• Phenanthrenes (pharmacology, therapeutic use)
• Phosphorylation
• Polymerization (drug effects)
• Prostatic Neoplasms (metabolism, pathology)
• Pseudopodia (metabolism)
• Tumor Cells, Cultured
• rac1 GTP-Binding Protein (antagonists & inhibitors, physiology)