23-hydroxyursolic acid causes cell growth-inhibition by inducing caspase-dependent apoptosis in human cervical squamous carcinoma HeLa cells.
BACKGROUND
There are few reports on the biological activities of 23-hydroxyursolic acid (23-HUA). The mechanism of growth-inhibition induced by 23-HUA, isolated from Cussonia bancoensis, in human cervical squamous carcinoma HeLa cells is hereby investigated.


METHODS
The growth-inhibitory activity was measured by MTS assay. Caspases activation and expression of apoptosis-related proteins were detected by Western blotting. Apoptotic cells were observed by morphological analysis with Hoechst 33342.


RESULTS
23-HUA inhibited the growth of HeLa cells in a concentration dependent manner. Proteolytically generated fragments of caspase-3, -8 and -9 were observed in HeLa cells treated with 60 microM 23-HUA. The expression of Bcl-X(L), an anti-apoptotic protein, was markedly decreased by 60 microM 23-HUA. Morphological analysis showed that apoptotic changes occurred after treatment with 60 microM 23-HUA, and the changes were inhibited by a pan-caspase inhibitor, Z-VAD-FMK.


CONCLUSIONS
These results indicate that 23-HUA causes potent growth-inhibition by the induction of apoptosis via activation of caspases in HeLa cells.
Takaya
Makiko
M
Department of Clinical Pharmacology, Hokuriku University, Kanazawa. Ishikawa 920-1181, Japan.
Nomura
Masaaki
M
Takahashi
Tatsuo
T
Kondo
Yoko
Y
Lee
Kyung-Tae
KT
Kobayashi
Shinjiro
S
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism*; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism; D005260:Female; D006367:HeLa Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D014315:Triterpenes; C469884:23-hydroxyursolic acid; D020169:Caspases