Ling, Dora and Marshall, Glenn M and Liu, Pei Y and Xu, Ning and Nelson, Charlotte A and Iismaa, Siiri E and Liu, Tao (2012) Enhancing the anticancer effect of the histone deacetylase inhibitor by activating transglutaminase. European Journal of Cancer, 48 (17). pp.3278-87. ISSN 1879-0852 (OA)
Ling, Dora and Marshall, Glenn M and Liu, Pei Y and Xu, Ning and Nelson, Charlotte A and Iismaa, Siiri E and Liu, Tao (2012) Enhancing the anticancer effect of the histone deacetylase inhibitor by activating transglutaminase. European Journal of Cancer, 48 (17). pp.3278-87. ISSN 1879-0852 (OA)
Ling, Dora and Marshall, Glenn M and Liu, Pei Y and Xu, Ning and Nelson, Charlotte A and Iismaa, Siiri E and Liu, Tao (2012) Enhancing the anticancer effect of the histone deacetylase inhibitor by activating transglutaminase. European Journal of Cancer, 48 (17). pp.3278-87. ISSN 1879-0852 (OA)
Abstract
Histone deacetylase (HDAC) inhibitors have shown promising anticancer effects in clinical trials. However, a proportion of patients do not respond to HDAC inhibitor therapy. We have previously demonstrated that tissue transglutaminase (TG2) is one of the genes commonly up-regulated by HDAC inhibitors in vitro and in vivo, and that two structurally distinct TG2 protein isoforms, the full-length (TG2-L) and the short form (TG2-S), exert opposing effects on cell differentiation due to difference in transamidation activity. Here we show that the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) transcriptionally activates the expression of both TG2-L and TG2-S, and that up-regulation of TG2-L renders neuroblastoma cells less sensitive to SAHA-induced cytotoxicity. Combination therapy with SAHA and the transamidation activator Naringenin, a natural product found in citrus fruits, synergistically enhanced transamidation activity and SAHA-induced cytotoxicity in neuroblastoma cells, but not in normal non-malignant cells. In tumour-bearing N-Myc transgenic mice, SAHA and Naringenin synergistically suppressed tumour progression. Taken together, our data demonstrate that SAHA-induced TG2-L over-expression renders cancer cells less sensitive to SAHA therapy, and suggest the addition of Naringenin to SAHA and probably also other HDAC inhibitors in future clinical trials in cancer patients. (NHMRC grants 568753, 459406 and 1006002; Cancer Institute NSW).
Metadata
Additional Information: | This article is available for free from the publisher's website |
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Subjects: | R Medicine > R Medicine (General) |
Depositing User: | Repository Administrator |
Date Deposited: | 04 Jan 2016 04:32 |
Last Modified: | 22 May 2018 04:53 |