β-Hydroxyisovalerylshikonin promotes reactive oxygen species production in HCT116 colon cancer cells, leading to caspase-mediated apoptosis

ABSTRACT Although β -hydroxyisovalerylshikonin is suggested as a potential therapeutic agent for preventing various cancers, the underlying molecular mechanisms are not completely understood. In the present study, we investigated whether β -hydroxyisovalerylshikonin enhances apoptosis by triggering reactive oxygen species production in colon cancer HCT116 cells. β -Hydroxyisovalerylshikonin significantly inhibited the viability of HCT116 cells with maximum inhibition at 4 µM. Furthermore, treatment with β -hydroxyisovalerylshikonin subsequently increased sub-G1 cells and annexin-V+ cell population. Additionally, pretreatment with the caspase-8 inhibitor, z-IETD-fmk, and the caspase-9 inhibitor, z-LETD-fmk, significantly decreased β -hydroxyisovalerylshikonin-induced apoptosis, suggesting that β -hydroxyisovalerylshikonin promotes apoptosis through both the intrinsic and the extrinsic apoptotic pathways by activating caspase-8 and caspase-9. We also found that mitochondria played an important role in β -hydroxyisovalerylshikonin-mediated apoptosis via the intrinsic pathway. Accordingly, β -hydroxyisovalerylshikonin-induced reactive oxygen species production was evident after treatment with β -hydroxyisovalerylshikonin, and pretreatment with reactive oxygen species inhibitors, N-acetyl-L-cysteine and glutathione, significantly decreased β -hydroxyisovalerylshikonin-induced reactive oxygen species production, resulting in inhibition of apoptosis, which suggests that R...

Source: Revista Brasileira de Farmacognosia - July 10, 2018 Category: Drugs & Pharmacology Source Type: research