Antiproliferative effects of α-tomatine are associated with different cell death modalities in human colon cancer cells

Antitumour effects of alpha-tomatine were studied during 24 hours in a panel of human colon cancer cells. alpha-Tomatine proved to induce dose-dependent cytotoxicity resulting in morphologically varying cell demise with predominantly occurring necrotic phenotypes and minor presence of cells dying via caspase-independent apoptosis. Analyses into the nature of mechanisms responsible for activation of cell death revealed that following alpha-tomatine treatment, changes in RIP3 and RIP1 protein expression take place along with cyclophilin D mitochondrial accumulation. Moreover, in treated cells, lysosomal membrane permeabilization as well as mitochondrial perturbation with subsequent mitochondrial release of apoptosisinducing factor (AIF) contributes to the execution of diverse death phenotypes possibly via enhanced activity JNK but in the absence of significant oxidative stress. Thus alpha-tomatine exhibits significant antitumour activity in colon cancer cells via targeting their membranous compartments and inducing both necroptosis and apoptosis. (C) 2016 Elsevier Ltd. All rights reserved.