Anti-angiogenic activity of melatonin in advanced cancer patients.
OBJECTIVE
The anticancer activity of the indole melatonin has been explained to be due to its immunomodulatory, anti-prolferative and anti-oxidant effects, whereas at present no data are available about its possible influence on the angiogenesis, which has been shown to be one of the main biological mechanisms responsible for tumor dissemination. Vascular endothelial growth factor (VEGF) is the most active angiogenic factor, and the evidence of abnormally high blood levels or VEGF has been proven to be associated with poor prognosis in cancer patients. To investigate the influence of melatonin on angiogenesis, in this preliminary study we have evaluated the effects of melatonin therapy on VEGF blood levels in advanced cancer patients.


METHODS
The study included 20 metastatic patients, who progressed on previous conventional antitumor therapies and for whom no other effective treatment was available. Melatonin was given orally at 20 mg/day in the evening for at least 2 months. Serum levels of VEGF were measured by an enzyme immunoassay on venous blood samples collected at 15-day intervals.


RESULTS
The clinical response consisted of minor response (MR) in 2, stable disease (SD) in 6 and progressive disease (PD) in the remaining 12 patients. VEGF mean levels decreased on therapy, without, however, statistical differences with respect to the pre-treatment values. In contrast, by evaluating changes in VEGF levels in relation to the clinical response, non-progressing patients (MR + SD) showed a significant decline in VEGF mean concentrations, whereas no effect was achieved in progressing patients.


CONCLUSIONS
This study, by showing that melatonin-induced control or the neoplastic growth is associated with a decline in VEGF secretion, would suggest that the pineal hormone may control tumor growth at least in part by acting as a natural anti-angiogenic molecule, with a following opposition or angiogenesis-dependent cancer proliferation.
Lissoni
P
P
Division of Radiation Oncology, San Gerardo Hospital, 20052 Monza, Milan, Italy.
Rovelli
F
F
Malugani
F
F
Bucovec
R
R
Conti
A
A
Maestroni
G J
GJ
D000328:Adult; D000368:Aged; D001859:Bone Neoplasms / Q000556:secondary; D002277:Carcinoma / Q000097:blood* / Q000188:drug therapy* / Q000556:secondary; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000188:drug therapy / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy / Q000556:secondary; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000188:drug therapy; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy; D018450:Disease Progression; D016228:Endothelial Growth Factors / Q000097:blood*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000097:blood / Q000188:drug therapy; D008113:Liver Neoplasms / Q000097:blood / Q000188:drug therapy / Q000556:secondary; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy / Q000556:secondary; D008222:Lymphokines / Q000097:blood*; D008297:Male; D008550:Melatonin / Q000627:therapeutic use*; D008875:Middle Aged; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D008550:Melatonin