In this study, we investigated the effects of
melatonin on
adriamycin-induced
cardiotoxicity both in vivo in rats and in vitro, and on the antitumor activities of
adriamycin on MDA-231 and NCI
breast cancer cells. Rats that received a single
intraperitoneal injection of 25 mg/kg
adriamycin showed a mortality rate of 86%, which was reduced to 20% by
melatonin treatment (10 mg/kg, SC for 6 days).
Melatonin attenuated
adriamycin-induced
body-weight loss, hemodynamic dysfunction, and the morphologic and biochemical alterations caused by
adriamycin.
Melatonin also reduced
adriamycin-induced nuclear DNA fragmentation, as assessed by the comet assay. In addition, the antitumor activity of
adriamycin could be maintained using lower doses of this drug in combination with
melatonin.
Melatonin treatment in the concentration range of 0.1-2.5 mM inhibited the growth of human
breast cancer cells. In terms of oncolytic activity, the combination of
adriamycin and
melatonin improved the antitumor activity of
adriamycin, as indicated by an increase in the number of long-term survivors as well as decreases in
body-weight losses resulting from
adriamycin treatment. These results indicate that
melatonin not only protects against
adriamycin-induced
cardiotoxicity but also enhances its antitumor activity. This combination of
melatonin and
adriamycin represents a potentially useful regimen for the treatment of human
neoplasms because it allows the use of lower doses of
adriamycin, thereby avoiding the toxic side effects associated with this drug.