KRN5500, a novel antitumor agent, induces apoptosis or cell differentiation in HL-60 cells

✍ Scribed by Kozo Kawasaki; Tomoyuki Murakami; Masamichi Ita; Kohsuke Sasaki; Susumu Furukawa

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 210 KB
• Volume: 39
• Category: Article
• ISSN: 0196-4763
• DOI: 10.1002/(sici)1097-0320(20000301)39:3<211::aid-cyto6>3.0.co;2-v

✦ Synopsis

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.