Calcium-mediated activation of PI3K and p53 leads to apoptosis in thyroid carcinoma cells |
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| Authors: | Z-M Liu G G Chen A C Vlantis G M Tse C K Y Shum C A van Hasselt |
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| Institution: | (1) Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong, China;(2) Department of Biochemistry and Molecular Biology, The School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, Sichuan, China;(3) Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong, China |
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| Abstract: | The molecular mechanism responsible for cadmium-induced cell death in thyroid cancer cells (FRO) is unknown. We demonstrated
that apoptosis of FRO cells induced by cadmium was concentration and time dependent. Cadmium caused the rapid elevation of
intracellular calcium and induced phosphorylation of Akt, p53, JNK, ERK and p38. Inhibition of PI3K/Akt attenuated the cadmium-induced
apoptosis, but the inhibition of JNK inhibitor, ERK or p38 aggravated it, indicating that activation of PI3K/Akt was a pro-apoptosis
signal in response to cadmium treatment, whereas the activation of stress-activated protein kinase JNK, ERK and p38 functioned
as survival signals to counteract the cadmium-induced apoptosis. Buffering of the calcium response attenuated mitochondrial
impairment, recovered the cadmium-activated Akt, p53, JNK, ERK and p38, and subsequently blocked the apoptosis. These results
suggested that apoptosis induced by cadmium in FRO cells was initiated by the rapid elevation of intracellular calcium, followed
by calcium-mediated activation of PI3K/Akt and mitochondrial impairment.
Received 28 February 2007; received after revision 2 April 2007; accepted 23 April 2007 |
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| Keywords: | Apoptosis cadmium calcium PI3K/Akt p53 thyroid cancer |
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