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Inhibition of apoptosis in human tumour cells by okadaic acid

โœ Scribed by Qizhong Song; Glenn D. Baxter; Eva M. Kovacs; Duygu Findik; Martin F. Lavin

Publisher
John Wiley and Sons
Year
1992
Tongue
English
Weight
741 KB
Volume
153
Category
Article
ISSN
0021-9541

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โœฆ Synopsis

Gamma-radiation, tetrandrine, bistratene A, and cisplatin were all found to induce pronounced morphological changes characteristic of apoptosis and extensive DNA fragmentation in the human EM13674 cell line 8 h after treatment.

Apoptosis induced in BMI 3674 cells by these diverse agents was markedly inhibited by 1 pM okadaic acid, a tumour promoter that inhibits protein phosphatases 1 and ZA. This compound also inhibitcd the appearance of apoptosis in fresh human leukaemia cells that had been exposed to gamma-radiation. The inhibition of apoptosk was confirmed using f l u u r e ~e n c e microscopy and DNA gel electrophoresis. Dephosphorylation of a limited number of proteins was shown to be associated with apoptosis and okadaic acid prevented these dephosphorylations.

Previous studies on the BM13674 cell line showed that an inhibitor of protein synthesis failed to prevent apoptosis in these cells. The present data providcs further support that posttranslational modification of proteins, in particular, phosphorylation/dephosphorylation status, plays an important role in inhibition/ activation of programmed cell death in different human cells after exposure to several cytotoxic agents.

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