Structures of isothiocyanates attributed to reactive oxygen species generation and microtubule depolymerization in HepG2 cells.

ABSTRACT

The structure of the isothiocyanates (ITCs)-erucin, sulforaphane, erysolin, sulforaphene, and phenethyl isothiocyanate-were assessed as well as their respective in vitro anticancer activity on the hepatocellular carcinoma cell line HepG2. All of these ITCs induced both apoptotic and necrotic cell death. FTIR analysis indicated that the ITCs caused changes in cellular components comparable to vinblastine. Despite no observable effect on DNA, the ITCs all induced generation of intracellular reactive oxygen species (ROS) and suppressed microtubule polymerization. The variation in sulfur oxidation states and the presence of an aromatic ring on the ITC side chain affected microtubule depolymerization and intracellular ROS generation, leading to apoptotic and necrotic cancer cell death. Knowing the influences of structural variations of the ITC side chain would be useful for selecting the more potent ITCs (i.e., erysolin) for the design and development of effective chemopreventive agents.