Protective effect of melatonin on human peripheral blood hematopoeitic stem cells against doxorubicin cytotoxicity.
BACKGROUND
The dose-limiting toxicity of doxorubicin on hematopoietic stem cells reduces the maximum benefit from this powerful drug. Melatonin may play a role in reducing this toxicity.


METHODS
Melatonin at 10 microM was used while challenging human peripheral blood stem cells (PBSC) with doxorubicin (0.6 microM and 1 microM), and colony formation was used to evaluate the protective effect of melatonin.


RESULTS
Melatonin was protective for the myeloid and erythroid series when given during or 1 hour after, but not before, doxorubicin, as measured by colony assay. This protection was independent from its antioxidant function as measured by 2', 7'-dichlodihydro-fluorescein diacetate and was selective for PBSC when compared to the MCF-7 cancer cell line.


CONCLUSIONS
The results suggest the importance of the time sequence for melatonin administration to exert its protective effect in relation to doxorubicin treatment, as well as its protective effect on both erythroid and myeloid elements independent from its antioxidant function.
Greish
Khaled
K
Department of Cardiovascular Surgery, Kumamoto University Graduate School of Medical Sciences, Japan.
Sanada
Isao
I
Saad
Alla El-Dein
Ael-D
Hasanin
Ehab
E
Kawasuji
Michio
M
Kawano
Fumio
F
Maeda
Hiroshi
H
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology / Q000633:toxicity*; D004347:Drug Interactions; D006402:Hematologic Diseases / Q000139:chemically induced / Q000517:prevention & control; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008550:Melatonin / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D017382:Reactive Oxygen Species; D004317:Doxorubicin; D006861:Hydrogen Peroxide; D008550:Melatonin