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

• Autor(a) principal: Dilshara,Matharage Gayani
• Data de Publicação: 2018
• Outros Autores: Karunarathne,Wisurumuni Arachchilage Hasitha Maduranga, Molagoda,Ilandarage Menu Neelaka, Kang,Chang-Hee, Jeong,Jin-Woo, Choi,Yung Hyun, Kim,Gi-Young
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Revista Brasileira de Farmacognosia (Online)
• Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0102-695X2018000300344
• topic: β-Hydroxyisovalerylshikonin; Apoptosis; Caspase; Reactive oxygen species

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 ROS generation is required for β-hydroxyisovalerylshikonin-mediated apoptosis. Taken together, these results demonstrated that the apoptotic effect of β-hydroxyisovalerylshikonin is enhanced in colon cancer HCT116 cells via reactive oxygen species generation and triggering of the caspase pathways, indicating that β-hydroxyisovalerylshikonin has potential as a therapeutic in the treatment of colon cancers.