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β-Hydroxyisovalerylshikonin promotes reactive oxygen species production in HCT116 colon cancer cells, leading to caspase-mediated apoptosis
Dilshara, Matharage Gayani; Karunarathne, Wisurumuni Arachchilage Hasitha Maduranga; Molagoda, Ilandarage Menu Neelaka; Kang, Chang-Hee; Jeong, Jin-Woo; Choi, Yung Hyun; Kim, Gi-Young.
  • Dilshara, Matharage Gayani; Jeju National University. Department of Marine Life Sciences. Jeju-si. KR
  • Karunarathne, Wisurumuni Arachchilage Hasitha Maduranga; Jeju National University. Department of Marine Life Sciences. Jeju-si. KR
  • Molagoda, Ilandarage Menu Neelaka; Jeju National University. Department of Marine Life Sciences. Jeju-si. KR
  • Kang, Chang-Hee; Nakdonggang National Institute of Biological Resource. Sangju-si. KR
  • Jeong, Jin-Woo; Nakdonggang National Institute of Biological Resource. Sangju-si. KR
  • Choi, Yung Hyun; Dong-Eui University. College of Oriental Medicine. Department of Biochemistry. Busan. KR
  • Kim, Gi-Young; Jeju National University. Department of Marine Life Sciences. Jeju-si. KR
Rev. bras. farmacogn ; 28(3): 344-351, May-June 2018. graf
Artigo em Inglês | LILACS | ID: biblio-958867
ABSTRACT
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.


Texto completo: DisponíveL Índice: LILACS (Américas) Idioma: Inglês Revista: Rev. bras. farmacogn Assunto da revista: Farmácia Ano de publicação: 2018 Tipo de documento: Artigo País de afiliação: Coréia do Sul Instituição/País de afiliação: Dong-Eui University/KR / Jeju National University/KR / Nakdonggang National Institute of Biological Resource/KR

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Texto completo: DisponíveL Índice: LILACS (Américas) Idioma: Inglês Revista: Rev. bras. farmacogn Assunto da revista: Farmácia Ano de publicação: 2018 Tipo de documento: Artigo País de afiliação: Coréia do Sul Instituição/País de afiliação: Dong-Eui University/KR / Jeju National University/KR / Nakdonggang National Institute of Biological Resource/KR