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Cancer Lett. 2009 Jan 18;273(2):243-9. doi: 10.1016/j.canlet.2008.08.015. Epub 2008 Sep 19.

Glucosamine is an effective chemo-sensitizer via transglutaminase 2 inhibition.

Author information

1
Molecular Oncology Branch, Division of Basic and Applied Sciences, Research Institute National Cancer Center, Goyang, Gyeonggi-do 410-769, Republic of Korea.

Abstract

Aberrant increases of transglutaminase 2 (TGase 2) in tumors contribute to drug resistance. The role of TGase 2 in cancer pathogenesis was unknown until we showed that TGase 2 activates NF-kappaB in the absence of kinase-dependent phosphorylation. It appears that increased expression of TGase 2 is responsible for the constitutive activation of NF-kappaB in cancer cells. We have demonstrated that TGase 2 inhibition using siRNA, cystamine or R2 peptide promotes cell death in drug-resistant cancer cells through NF-kappaB inactivation. Therefore, a safe and effective small molecule for TGase 2 inhibition is being sought in the development of therapeutics for malignant cancers. By screening for TGase inhibitors in a natural compound library, we found that glucosamine has a TGase 2 inhibitory effect in vitro. Glucosamine also recovered the depletion of I-kappaBalpha via TGase 2 inhibition, which resulted in a decrease of NF-kappaB activity in EcR293/TG cells. Furthermore, glucosamine efficiently promoted cell death via inhibiting TGase 2-mediated NF-kappaB activation in drug-resistant breast cancer cells. These results suggest that glucosamine, as a TGase 2 inhibitor, might be an attractive novel target for treatment of malignant cancers.

PMID:
18804908
DOI:
10.1016/j.canlet.2008.08.015
[Indexed for MEDLINE]

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