Isoegomaketone induces apoptosis in SK-MEL-2 human melanoma cells through mitochondrial apoptotic pathway via activating the PI3K/Akt pathway

Kwon,Soon-Jae; Lee,Ju-Hye; Moon,Kwang-Deog; Jeong,Il-Yun; Yee,Sung-Tae; Lee,Mi-Kyung; Seo,Kwon-Il

doi:10.3892/ijo.2014.2598

Isoegomaketone induces apoptosis in SK-MEL-2 human melanoma cells through mitochondrial apoptotic pathway via activating the PI3K/Akt pathway

Authors:
- Soon-Jae Kwon
- Ju-Hye Lee
- Kwang-Deog Moon
- Il-Yun Jeong
- Sung-Tae Yee
- Mi-Kyung Lee
- Kwon-Il Seo
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Affiliations: Department of Food Science and Technology, Kyungpook National University, Daegu 702-701, Republic of Korea, Department of Food and Nutrition, Sunchon National University, Suncheon, Jeonnam 540-742, Republic of Korea, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, Jeonbuk 580-185, Republic of Korea, Department of Biology, Sunchon National University, Suncheon, Jeonnam 540-742, Republic of Korea
Published online on: August 14, 2014 https://doi.org/10.3892/ijo.2014.2598
Pages: 1969-1976

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Abstract

Isoegomaketone (IK) is a major biologically active component of Perilla frutescens. In this study, we investigated the contribution of reactive oxygen species (ROS) to IK-induced apoptosis in human melanoma SK-MEL-2 cells. We found that IK inhibited the proliferation of SK-MEL-2 human melanoma cells in a dose-dependent manner. IK also induced sub-G1 DNA accumulation, formation of apoptotic bodies, nuclear condensation, and a DNA ladder in SK-MEL-2 cells. IK also induced activation of caspase-3 and -9, whereas caspase‑8 was unaffected. Further, N-acetyl-L-cysteine (NAC, ROS scavenger) treatment to SK-MEL-2 cells significantly reduced IK-induced cell death. Pretreatment of NAC to SK-MEL-2 cells followed by 100 µM IK reduced the protein levels of Bax and cytochrome c as well as PARP cleavage, whereas the protein level of Bcl-2 increased. Moreover, IK inhibited the phosphorylation of AKT/mTOR protein and cell proliferation induced by LY294002, a PI3K inhibitor. In conclusion, IK-induced ROS generation regulates cell growth inhibition and it induces apoptosis through caspase‑dependent and -independent pathways via modulation of PI3K/AKT signaling in SK-MEL-2 cells.

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