Herbal compound triptolide synergistically enhanced antitumor activity of vasostatin120-180.

Abstract

Angiogenesis is essential for the survival and growth of most tumors. As such, targeting the tumor neovasculature is an attractive strategy for effective cancer therapy. Angiogenesis inhibitors have strong therapeutic potential as antitumor agents in suppressing tumor growth and metastatic progression. The functional domain within amino acid residues 120-180 of vasostatin (VAS) has been confirmed to be effective in inhibiting the proliferation, migration, and invasiveness of cancer cells by its suppressive capacity against angiogenesis. Triptolide (TPL) is an active component extracted from the traditional Chinese herbal medicine Tripterygium wilfordii Hook F that has shown antitumor activities in various cancer cell types. However, its therapeutic application is limited by its toxicity in normal tissues and complications caused in patients. In this study, we attempted to investigate the synergistic antitumor activity of TPL and VAS in solid tumor cells. Our results showed that the sensitivity of combined therapy using TPL and VAS was higher than that of monotherapy using TPL or VAS. Apoptosis induced by the combined treatment was accompanied by activation of caspase-9, caspase-8, and caspase-3. Upregulation of proapoptotic protein (Bax, Bak, and Bad) expression and suppression of NF-κB transcriptional activity and its targeting antiapoptotic genes (c-FLIP, cIAP, Bcl-2, Bcl-xl, and Mcl-1) may contribute to the synergistic effects of this combination therapy. Further, using a mouse xenograft model, we demonstrated that combined treatment completely suppressed tumor growth as compared with treatment with TPL or VAS alone. These results suggest that the combination of TPL and VAS at lower concentrations may produce a synergistic antitumor effect that warrants further investigation for its potential clinical applications.

• Authors: Yuli Lin, Xuguang Yang, Min Lu, Weijuan Zheng, Jing Zhang, Hongqin Zhuang, Zi-Chun Hua
• Journal: Anti-cancer drugs (Anticancer Drugs) Vol. 24 Issue 9 Pg. 945-57 (Oct 2013) ISSN: 1473-5741 [Electronic] England
• PMID: 23958791 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• Antineoplastic Agents, Phytogenic
• Calreticulin
• Diterpenes
• Drugs, Chinese Herbal
• Epoxy Compounds
• Peptide Fragments
• Phenanthrenes
• Recombinant Proteins
• vasostatin
• triptolide

Topics

• Angiogenesis Inhibitors (administration & dosage, genetics, pharmacology, therapeutic use)
• Animals
• Antineoplastic Agents, Phytogenic (administration & dosage, adverse effects, pharmacology, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects, pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Calreticulin (administration & dosage, genetics, pharmacology, therapeutic use)
• Cell Line
• Cell Line, Tumor
• Colorectal Neoplasms (blood supply, drug therapy, pathology)
• Diterpenes (administration & dosage, adverse effects, pharmacology, therapeutic use)
• Drug Synergism
• Drugs, Chinese Herbal (chemistry)
• Epoxy Compounds (administration & dosage, adverse effects, pharmacology, therapeutic use)
• Ethnopharmacology
• HCT116 Cells
• Humans
• Mice
• Mice, Nude
• Neoplasms (blood supply, drug therapy, pathology)
• Neovascularization, Pathologic (prevention & control)
• Peptide Fragments (administration & dosage, genetics, pharmacology, therapeutic use)
• Phenanthrenes (administration & dosage, adverse effects, pharmacology, therapeutic use)
• Random Allocation
• Recombinant Proteins (administration & dosage, adverse effects, pharmacology, therapeutic use)
• Tripterygium (chemistry)
• Xenograft Model Antitumor Assays