KRN5500, a novel antitumor agent, induces apoptosis or cell differentiation in HL-60 cells.
BACKGROUND
KRN5500, a derivative of spicamycin, shows antitumor activity against a variety of tumor cell lines. However, the mechanism of cytotoxic action has remained unclear.


METHODS
The viability of HL-60 human leukemic cells treated with KRN5500 was studied by the dye exclusion assay. Induction of apoptosis and effects on the cell cycle were investigated by flow cytometry: We measured cellular DNA content after extraction of fragmented DNA, and apoptosis-induced DNA strand breaks. Cell morphology was observed by light microscopy. DNA strand breaks at a nucleosomal unit were analyzed by electrophoresis.


RESULTS
Our data demonstrated that KRN5500 caused inhibition of cell growth, and that apoptosis was the mode of cell death. G(1) phase cells were more susceptible to KRN5500 induced apoptosis. In addition, KRN5500 induced cell differentiation at lower concentration.


CONCLUSIONS
It is anticipated that KRN5500 will be used clinically as an anti-leukemic agent. Its mechanism of antitumor action is to induce apoptosis or cell differentiation.
Kawasaki
K
K
Department of Pediatrics, Yamaguchi University School of Medicine, Ube, Japan. kozok@d2.dion.ne.jp
Murakami
T
T
Ita
M
M
Sasaki
K
K
Furukawa
S
S
D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004273:DNA, Neoplasm / Q000302:isolation & purification; D005434:Flow Cytometry / Q000379:methods; D018922:HL-60 Cells; D006801:Humans; D007700:Kinetics; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects*; D011684:Purine Nucleosides / Q000633:toxicity; D013997:Time Factors
D000903:Antibiotics, Antineoplastic; D004273:DNA, Neoplasm; D011684:Purine Nucleosides; C092296:KRN 5500