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Title: Heparin/heparan sulfate interacting protein plays a role in apoptosis induced by anticancer drugs
Authors: Liu, J-J. 
Zhang, J.
Ramanan, S. 
Julian, J.-A.
Carson, D.D.
Hooi, S.C. 
Issue Date: Jun-2004
Citation: Liu, J-J., Zhang, J., Ramanan, S., Julian, J.-A., Carson, D.D., Hooi, S.C. (2004-06). Heparin/heparan sulfate interacting protein plays a role in apoptosis induced by anticancer drugs. Carcinogenesis 25 (6) : 873-879. ScholarBank@NUS Repository.
Abstract: 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. © Oxford University Press 2004; all rights reserved.
Source Title: Carcinogenesis
ISSN: 01433334
DOI: 10.1093/carcin/bgh081
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