Antitumour action of 5,6-dimethylxanthenone-4-acetic acid in rats bearing chemically induced primary mammary tumours.

Abstract

PURPOSE:

To evaluate the antitumour activity of 5,6-dimethylxanthenone-4-acetic acid (DMXAA), a vascular disrupting agent currently under phase II clinical trials in combination with cancer chemotherapy, in rats bearing chemically induced primary mammary tumours.

METHODS:

Tumours were induced in female Wistar rats by injection of N-nitroso-N-methylurea at 100 mg/kg subcutaneously. A clinically relevant single dose of DMXAA (1,800 mg/m(2)) was given to animals when tumours were measurable. Tumour volume, extent of necrosis and cytokine profiles were measured.

RESULTS:

Compared with the control group, DMXAA treatment significantly delayed tumour doubling time and extended the time from treatment to euthanasia. Four of five DMXAA-treated animals showed necrosis involving 3.7-41.2% of the area of the tumour section at 24 h compared with none of four control animals (P < 0.028, Chi-square test). Intratumoural levels of TNFalpha, IL-6, VEGF and IL-1alpha were increased 4 h after DMXAA treatment.

CONCLUSIONS:

This study shows for the first time that DMXAA has significant in vivo antitumour activity against non-transplanted autochthonous tumours and in a host species other than the mouse.

• Authors: Johnson J Liu, Lai-Ming Ching, Michael Goldthorpe, Rachel Sutherland, Bruce C Baguley, James A Kirker, Mark J McKeage
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 59 Issue 5 Pg. 661-9 (Apr 2007) ISSN: 0344-5704 [Print] Germany
• PMID: 16944150 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Carcinogens
• Cytokines
• Xanthones
• vadimezan
• Methylnitrosourea

Topics

• Animals
• Antineoplastic Agents (therapeutic use)
• Apoptosis (drug effects)
• Carcinogens
• Cytokines (biosynthesis)
• Female
• Immunoassay
• In Situ Nick-End Labeling
• Mammary Neoplasms, Experimental (chemically induced, drug therapy, pathology)
• Methylnitrosourea
• Rats
• Xanthones (therapeutic use)