beta-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.

Abstract:

:beta-Hydroxyisovalerylshikonin (beta-HIVS), which was isolated from the plant, Lithospermium 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 beta-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 beta-HIVS were the remarkable morphological changes induced upon treatment of HL-60 cells with beta-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 beta-HIVS 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 beta-HIVS was not inhibited by inhibitors of caspases, suggesting that JNK is located either upstream or independent of the caspase signaling pathway. beta-HIVS did not inhibit the activity of topoisomerase II. These results indicate that beta-HIVS induces apoptosis in HL-60 cells through a mechanism unlike those reported for anti-Fas antibodies and etoposide.

journal_name

J Biochem

journal_title

Journal of biochemistry

authors

Hashimoto S,Xu M,Masuda Y,Aiuchi T,Nakajo S,Cao J,Miyakoshi M,Ida Y,Nakaya K

doi

10.1093/oxfordjournals.jbchem.a022255

subject

Has Abstract

pub_date

1999-01-01 00:00:00

pages

17-23

issue

1

eissn

0021-924X

issn

1756-2651

journal_volume

125

pub_type

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