Antiangiogenic activities and cisplatin-combined antitumor activities of BPR0L075.

Abstract

BACKGROUND:

Antimitotic tubulin-binding BPR0L075 is structurally analogous to the vascular-disrupting combretastatin A-4.

MATERIALS AND METHODS:

In vitro/in vivo models of endothelial cells cultures, Matrigel plug assay, tumor-bearing nude mice, and murine leukemia cells-inoculated mice were utilized to evaluate BPR0L075 for antiangiogenic and antitumoral activity spectra.

RESULTS:

BPR0L075 concentration-dependently inhibited proliferation and migration of human umbilical vein endothelial cells (HUVECs), disrupted capillary tube formations of HUVECs and rat aorta endothelial cells, and suppressed in vivo VEGF-mediated angiogenesis in Matrigel plugs in mice. Besides inhibiting the colony growth of cancer cells, BPR0L075 suppressed growth of subcutaneously-xenografted human lung, colorectal, and cervical solid tumors in nude mice. Combination treatments of BPR0L075 plus cisplatin, compared to either agent alone, demonstrated a stronger growth inhibition against the tumor xenografts in nude mice and longer lifespan in the leukemia mice.

CONCLUSION:

BPR0L075 is an antitumoral and antiangiogenic agent and potentiates the anticancer activity of cisplatin.

• Authors: Ching-Ping Chen, Chih-Bo Hu, Kai-Chia Yeh, Jen-Shin Song, Teng-Kuang Yeh, Fei-Feng Tung, Ling-Ling Hwang, Huan-Yi Tseng, Yu-Chen Huang, Horng-Shing Shy, Su-Huei Hsieh, Chien-Chang Shen, Hsin-Sheng Wang, Hsing-Pang Hsieh, Jing-Ping Liou, Yu-Sheng Chao, Chiung-Tong Chen
• Journal: Anticancer research (Anticancer Res) Vol. 30 Issue 7 Pg. 2813-22 (Jul 2010) ISSN: 1791-7530 [Electronic] Greece
• PMID: 20683017 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 6-methoxy-3-(3',4',5'-trimethoxybenzoyl)-1H-indole
• Angiogenesis Inhibitors
• Indoles
• Cisplatin

Topics

• Angiogenesis Inhibitors (administration & dosage, pharmacology)
• Animals
• Antineoplastic Combined Chemotherapy Protocols (pharmacology)
• Cell Growth Processes (drug effects)
• Cisplatin (administration & dosage)
• Drug Screening Assays, Antitumor
• Drug Synergism
• Endothelial Cells (drug effects)
• Female
• HCT116 Cells
• Humans
• Indoles (administration & dosage, pharmacology)
• Leukemia P388 (drug therapy)
• Male
• Mice
• Mice, Inbred DBA
• Mice, Nude
• Neoplasms (drug therapy, pathology)
• Rats
• Rats, Sprague-Dawley
• Xenograft Model Antitumor Assays