Luteolin induces apoptotic cell death via antioxidant activity in human colon cancer cells

Kang,Kyoung Ah; Piao,Mei Jing; Ryu,Yea Seong; Hyun,Yu Jae; Park,Jeong Eon; Shilnikova,Kristina; Zhen,Ao Xuan; Kang,Hee Kyoung; Koh,Young Sang; Jeong,Yong Joo; Hyun,Jin Won

doi:10.3892/ijo.2017.4091

Luteolin induces apoptotic cell death via antioxidant activity in human colon cancer cells

Authors:
- Kyoung Ah Kang
- Mei Jing Piao
- Yea Seong Ryu
- Yu Jae Hyun
- Jeong Eon Park
- Kristina Shilnikova
- Ao Xuan Zhen
- Hee Kyoung Kang
- Young Sang Koh
- Yong Joo Jeong
- Jin Won Hyun
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Affiliations: Department of Biochemistry, School of Medicine and Jeju Research Center for Natural Medicine, Jeju National University, Jeju 63243, Republic of Korea, Department of Bio and Nanochemistry, Kookmin University, Seoul 02707, Republic of Korea
Published online on: August 2, 2017 https://doi.org/10.3892/ijo.2017.4091
Pages: 1169-1178

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Abstract

The present study determined whether luteolin induces HT-29 colon cancer cell death through an antioxidant effect such as the activation of antioxidant enzymes. Luteolin decreased cell viability in human colon cancer cells (HT-29), whereas it had no effect on normal colon cells (FHC). Luteolin induced apoptosis by activating the mitochondria-mediated caspase pathway in HT-29 cells. Luteolin caused loss of the mitochondrial membrane action potential, increased mitochondrial Ca2+ level, upregulated Bax, downregulated Bcl-2, induced the release of cytochrome c from mitochondria to the cytosol, and increased the levels of the active forms of caspase-9 and caspase-3. Luteolin-induced apoptosis was accompanied by the activation of intracellular and mitochondrial reactive oxygen species scavenging through the activation of antioxidant enzymes, such as superoxide dismutase and catalase in HT-29 cells. Luteolin increased the level of reduced glutathione (GSH) and the expression of GSH synthetase, which catalyzes the second step of GSH biosynthesis. The apoptotic effect of luteolin was mediated by the activation of the mitogen-activated protein kinase signaling pathway. The present results indicate that luteolin induces apoptosis by promoting antioxidant activity and activating MAPK signaling in human colon cancer cells.

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