title: Induction of apoptosis by isoegomaketone from Perilla frutescens L. in B16 melanoma cells is mediated through ROS generation and mitochondrial-dependent, -independent pathway.
abstract: We have demonstrated for the first time the mechanism underlying ROS-mediated mitochondria-dependent apoptotic cell death triggered by isoegomaketone (IK) treatment in melanoma cells. We showed that IK induced apoptotic cell death and tumor growth inhibition using tissue culture and in vivo models of B16 melanoma. Furthermore, we observed that IK effectively induced apoptotic cell death, including sub-G1 contents up-regulation, nuclei condensation, DNA fragmentation, and caspase activation in B16 melanoma cells. Pretreatment with caspase inhibitor increased the survival rate of IK-treated B16 cells, implying that caspases play a role in IK-induced apoptosis. Furthermore, IK treatment generated ROS in melanoma cells. We also determined whether or not IK-induced cell death is due to ROS production in B16 cells. N-acetyl cysteine (NAC) inhibitedIK-induced Bcl-2 family-mediated apoptosis. This result indicates that IK-induced apoptosis involves ROS generation as well as up-regulation of Bax and Bcl-2 expression, leading to release of cytochrome c and AIF. Our data suggest that IK inhibits growth and induces apoptosis in melanoma cells via activation of ROS-mediated caspase-dependent and -independent pathways.
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, 413 Jungangno, 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 Animal Science, Iowa State University, Ames, IA 50011-3150, USA.
authors.forename: Dong-U K
authors.initials: DU
authors.lastname: Ahn
authors.affiliation: Department of Food and Nutrition, Sunchon National University, 413 Jungangno, 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, 413 Jungangno, Suncheon, Jeonnam 540-742, Republic of Korea. Electronic address: seoki@sunchon.ac.kr.
authors.forename: Kwon-Il
authors.initials: KI
authors.lastname: Seo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D005663:Furans / Q000494:pharmacology*; D007659:Ketones / Q000494:pharmacology*; D008546:Melanoma, Experimental / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D031344:Perilla frutescens / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D005663:Furans; D007659:Ketones; D017382:Reactive Oxygen Species; C568138:isoegomaketone; D020169:Caspases
keywords: Apoptosis; Apoptosis inducing factor; B16 melanoma cells; Isoegomaketone; Reactive oxygen species