Effects of the natural compound curcumin and its analogues DMC and EF24 in combination with TRAIL against kidney cancer

The natural compound Curcumin has been shown to have therapeutic potential against a wide range of diseases such as cancer. Curcumin reduces cell viability of renal cell carcinoma cells, when combined with TRAIL, a cytokine that specifically targets cancer cells, by helping overcome TRAIL resistance. However, its therapeutic effects are limited by its low bioavailability. Similar compounds to Curcumin with higher bioavailability, such as DMC and EF24, could potentially have similar anticancer effects and sensitise renal cell carcinoma cells to TRAIL-induced apoptosis. This study shows the effects of Curcumin and its analogues DMC and EF24 individually and in combination with TRAIL in the human kidney cancer cell line, ACHN, on the reduction of cell viability and induction of reactive oxygen species using MTT, LDH and flow cytometry assays. As a highly metastatic cancer type, the reduction of ACHN cell migration by Curcuminoids in combination with TRAIL was assessed through a scratch assay, paired with an MMP-2/MMP-9 activity assay. In order to better understand the mechanism of action behind these effects, protein expression was analysed through western blot and mass spectrometry, focusing mainly on the expression of pro- and anti-apoptotic proteins (Caspase 8, DR4, Bax, Bcl xl, Xiap) and other proteins that may play a role in apoptosis (such as p38 and JNK). Increases in pro-apoptotic protein expression and decreases in anti-apoptotic proteins were observed. This is the first study showing the effects of Curcuminoid analogues on a human renal cancer cell line.