title: Isoegomaketone induces apoptosis in SK-MEL-2 human melanoma cells through mitochondrial apoptotic pathway via activating the PI3K/Akt pathway.
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.
authors.affiliation: Department of Food Science and Technology, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Soon-Jae
authors.initials: SJ
authors.lastname: Kwon
authors.affiliation: Department of Food and Nutrition, Sunchon National University, Suncheon, Jeonnam 540-742, Republic of Korea.
authors.forename: Ju-Hye
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Food Science and Technology, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Kwang-Deog
authors.initials: KD
authors.lastname: Moon
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, Jeonbuk 580-185, Republic of Korea.
authors.forename: Il-Yun
authors.initials: IY
authors.lastname: Jeong
authors.affiliation: Department of Biology, Sunchon National University, Suncheon, Jeonnam 540-742, Republic of Korea.
authors.forename: Sung-Tae
authors.initials: ST
authors.lastname: Yee
authors.affiliation: Department of Food and Nutrition, Sunchon National University, Suncheon, Jeonnam 540-742, Republic of Korea.
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Lee
authors.affiliation: Department of Food and Nutrition, Sunchon National University, Suncheon, Jeonnam 540-742, Republic of Korea.
authors.forename: Kwon-Il
authors.initials: KI
authors.lastname: Seo
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002867:Chromones; D005663:Furans / Q000008:administration & dosage*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007659:Ketones / Q000008:administration & dosage*; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008928:Mitochondria / Q000235:genetics / Q000473:pathology; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis* / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000096:biosynthesis
chemical_list: D002867:Chromones; D005663:Furans; D007659:Ketones; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C568138:isoegomaketone; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C546842:MTOR protein, human