Membrane Association of the Short Transglutaminase Type 2 Splice Variant (TG2-S) Modulates Cisplatin Resistance in a Human Hepatocellular Carcinoma (HepG2) Cell Line.

Hepatocellular carcinoma (HCC) is a heterogeneous malignancy with complex carcinogenesis. Although there has been significant progress in the treatment of HCC over the past decades, drug resistance to chemotherapy remains a major obstacle in its successful management. In this study, we were able to reduce chemoresistance in cisplatin-resistant HepG2 cells by either silencing the expression of transglutaminase type 2 (TG2) using siRNA or by the pre-treatment of cells with the TG2 enzyme inhibitor cystamine.

Inhibition of Transglutaminase 2 activity increases cisplatin cytotoxicity in a model of human hepatocarcinoma chemotherapy.

Transglutaminase 2 (TG2) is a ubiquitous multifunctional enzyme whose expression has been found to be altered in numerous studies of apoptosis and cell survival; its activity has been found to be increased in many types of cancer, where it is often over-expressed. Cisplatin has long been used as an effective therapeutic drug to treat numerous cancers. Although its activity is based on cross-linking of DNA, cisplatin may also operate via other mechanisms that involve modification and alteration in the activity of protein and RNA modulators of the cell cycle and apoptotic processes; these mechanisms are less well characterised.