Nicaraven induces programmed cell death by distinct mechanisms according to the expression levels of Bcl-2 and poly (ADP-ribose) glycohydrolase in cancer cells

Transl Oncol. 2022 Oct 4;26:101548. doi: 10.1016/j.tranon.2022.101548. Online ahead of print.

Abstract

The PARP-1 expression level and poly (ADP-ribosyl)ation activity in cancer markedly affect the therapeutic outcome. Nicaraven, a free radical scavenger has been found to inhibit PARP, but the effect on cancer cells is still unclear. In this study, we investigated the potential role and molecular mechanism of nicaraven on cancer cells. Using U937 lymphoma cells and HCT-8 colorectal cancer cells, we found that nicaraven moderately reduced the cell viability of both cells in a dose-dependent manner. Interestingly, nicaraven significantly induced apoptosis of U937 cells that are dominantly expressing Bcl-2 but induced PAR-dependent cell death (parthanatos) of HCT-8 cells that are highly expressing poly (ADP-ribose) glycohydrolase (PARG). Based on our data, nicaraven seems to induce programmed cell death through distinct mechanisms, according to the expression levels of Bcl-2 and PARG in cancer cells.

Keywords: Apoptosis; Bcl-2; Cancer cells; Nicaraven; PARG; Parthanatos.