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- Title
ß-Hydroxyisovalerylshikonin Inhibits the Cell Growth of Various Cancer Cell Lines and Induces Apoptosis in Leukemia HL–60 Cells through a Mechanism Different from Those of Fas and Etoposide.
- Authors
Hashimoto, Sachiko; Xu, Man; Masuda, Yutaka; Aiuchi, Toshihiro; Nakajo, Shigeo; Cao, Judong; Miyakoshi, Masazumi; Ida, Yoshiteru; Nakaya, Kazuyasu
- Abstract
ß-Hydroxyisovalerylshikonin (ß-HIVS), which was isolated from the plant, Lithosper-mium radix, inhibited the growth of various lines of cancer cells derived from human solid, tumors at low concentrations between 10-8 and 10-6 M. When HL-60 cells were treated with 10-6 M ß-HIVS for 3 h, characteristic features of apoptosis, such as DNA fragmentation, nuclear fragmentation, and activation of caspase-3–like activity, were observed. The most characteristic features of the effect of ß-HIVS were the remarkable morphological changes induced upon treatment of HL-60 cells with ß-HIVS, as visualized on the staining of actin filaments with phalloidin labeled with tetramethylrhodamine B isothiocyanate. Moreover, activation of MAP kinases, such as ERK2, JNK and p38, was detected after treatment with 10-6 M ß-HTVS preceding the appearance of the characteristics of apoptosis, and the features of the activation of these MAP kinases were quite different from those of Fas and anticancer drug-induced apoptosis. The activation of JNK by ;ß-HIVS was not inhibited by inhibitors of caspases, suggesting that JNK is located either upstream or independent of the caspase signaling pathway. ß-HIVS did not inhibit the activity of topoisomerase II. These results indicate that ß-HIVS induces apoptosis in HL-60 cells through a mechanism unlike those reported for anti-Fas antibodies and etoposide.
- Subjects
APOPTOSIS; LEUKEMIA; ETOPOSIDE; LITHOSPERMUM; DNA
- Publication
Journal of Biochemistry, 1999, Vol 125, Issue 1, p17
- ISSN
0021-924X
- Publication type
Article
- DOI
10.1093/oxfordjournals.jbchem.a022255