Mitochondria and calpains mediate caspase-dependent apoptosis induced by doxycycline in HeLa cells |
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Authors: | J Wu T Liu J Xie F Xin L Guo |
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Institution: | (1) Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Room 901, Cell Biology Building, 320 Yueyang Road, Shanghai, 200031, China;(2) Graduate school of the Chinese Academy of Sciences, Beijing, China |
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Abstract: | Doxycycline (Dc) has been demonstrated to inhibit cell growth and induce apoptosis in tumor cells, although its mechanism
of action is not fully understood. The present study demonstrates that apoptosis can be induced in HeLa cells. Western blot
data demonstrated that cytochrome c (Cyt c), Smac (the second mitochondria-derived activator of caspase), calpain I, caspase-9,
−3 and −8 were involved in the apoptotic process, while the pan caspase inhibitor zVAD-fmk almost completely inhibited Dc-induced
apoptosis. We further demonstrated that the release of mitochondrial proteins and the activation of calpains occurred upstream
of the caspase cascade, in which caspase-9 was activated in response to the release of Cyt c, that caspase-8 activation was
caspase and calpain dependent, and that caspase-3 was activated mainly by caspase-8 and −9. Caspase-8 played important roles
in the activation of caspase-3 and induction of apoptosis, whereas the role of the caspase-9 was limited.
Received 26 November 2005; received after revision 14 February 2006; accepted 1 March 2006 |
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Keywords: | Doxycycline apoptosis mitochondria calpain caspase |
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