Carcinogenesis Advance Access originally published online on January 16, 2004
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Carcinogenesis, Vol. 25, No. 6, 873-879,
June 2004
Carcinogenesis vol.25 no.6 © Oxford University Press 2004; all rights reserved.
ARTICLE |
Heparin/heparan sulfate interacting protein plays a role in apoptosis induced by anticancer drugs
1 Department of Physiology, Faculty of Medicine, National University of Singapore, Republic of Singapore and 2 Department of Biological Science, University of Delaware, Newark, USA
3 To whom correspondence should be addressed. Email: phshsc{at}nus.edu.sg
Heparin/heparan sulfate interacting protein (HIP, also known as ribosome protein L29) is involved in cell–cell and cell–extracelluar matrix interactions and influences cell proliferation, migration and differentiation. In the present study, we investigated the role of HIP in anticancer drug-induced apoptosis. Both colon cancer HCT-116 and HT-29 cells showed dose-dependent down-regulation of HIP expression when treated with sodium butyrate. The down-regulation was negatively correlated with the percentage of apoptotic cells (R = –0.955, P = 0.03 and R = –0.792, P = 0.06 for HCT-116 and HT-29 cells, respectively). The correlation between HIP expression and apoptosis in HCT-116 cells was also evident in the differential expression of HIP in the floating and adherent cell populations. Most apoptotic cells were distributed in the floating population. HIP expression in this population was 
30% lower than adherent and untreated control cells. HIP expression in HCT-116 cells was also significantly decreased in parallel with apoptosis after treatment with 50 µM camptothecin and 20 µM 5-fluorouracil. This indicates that the down-regulation of HIP may be a general phenomenon in anticancer drug-induced apoptosis. The down-regulation of HIP occurred in the early phase of apoptosis, in parallel with the activation of caspase-3 and the externalization of phosphatidylserine. The functional significance of HIP in apoptosis was shown by knocking down the expression of HIP using small interfering RNA. A 50% reduction in HIP expression was sufficient to increase the percentage of apoptotic cells (from 11 to 20%) and increase the sensitivity of the cells to apoptosis induced by 1 mM butyrate by 60%. These results indicate that HIP may play an important role in anticancer drug-induced apoptosis.