Angiogenesis is an important therapeutic target in
cancer, and to fully exploit its therapeutic potential, combination chemotherapeutic/antiangiogenic regimens should be optimized and delivered earlier to more patients. Ideally, this could be done by a single potent oral agent with established safety.
Rifampicin, a semisynthetic
antibiotic derived from the
rifamycins, is one of the most commonly used pharmaceutical compounds worldwide in the treatment of
tuberculosis. Here, we present the effects of oral
rifampicin on human
cancer progression and its antiangiogenic properties, which were comparable to the
angiogenesis inhibitor endostatin. Clinically, low-dose p.o. administration of
rifampicin to six high-risk patients with hepatitis C virus-related
liver cirrhosis resulted in a single occurrence of
hepatocellular carcinoma during the follow-up period of 97.3 +/- 29.1 (mean +/- SD) months. Experimentally,
rifampicin rapidly and markedly down-regulated the expression of a wide spectrum of angiogenesis-associated genes in growing human microvascular endothelial cells, thereby suppressing endothelial cell proliferation and migration.
Rifampicin, at higher concentrations, also directly inhibited the growth of a variety of human
cancer cells. P.o. administration of
rifampicin significantly inhibited in vivo growth and
metastases of subcutaneous human
cancer xenografts. Thus, the potent antiangiogenic properties of oral
rifampicin therapy were effective in suppressing
cancer progression. It provides a promising new addition to antiangiogenic strategies for designing human
cancer therapies. Considering the clinical pharmacokinetics of
rifampicin, which enters the enterohepatic circulation and undergoes subsequent hepatic accumulation, it may be especially beneficial as an
antitumor agent targeting hepatobiliary
tumors.