title: Esculetin induces death of human colon cancer cells via the reactive oxygen species-mediated mitochondrial apoptosis pathway.
abstract: The present study investigated the apoptotic effects of esculetin, a coumarin derivative, on the human colon cancer cell line HT-29. Esculetin had cytotoxic effects on HT-29 cells in a dose- and time-dependent manner; treatment with 55 μg/mL esculetin reduced cell viability by 50%. Esculetin induced apoptosis, as evidenced by apoptotic body formation, an increased percentage of cells in sub-G1 phase, and DNA fragmentation. Moreover, esculetin increased mitochondrial membrane depolarization, released cytochrome c into cytosol, and modulated the expression of apoptosis-associated proteins, resulting in reduced expression of B cell lymphoma-2, increased expression of Bcl-2-associated X protein, and activation of caspase-9 and caspase-3. Esculetin induced the formation of reactive oxygen species; however, treatment with an antioxidant reduced the apoptotic cell death induced by esculetin treatment. In addition, esculetin activated mitogen-activated protein kinases and specific inhibitors of these kinases abrogated the reduction in cell viability induced by esculetin treatment.
authors.affiliation: School of Medicine, Jeju National University, Jeju 690-756, Republic of Korea.
authors.forename: Areum Daseul
authors.initials: AD
authors.lastname: Kim
authors.affiliation: School of Medicine, Jeju National University, Jeju 690-756, Republic of Korea.
authors.forename: Xia
authors.initials: X
authors.lastname: Han
authors.affiliation: School of Medicine, Jeju National University, Jeju 690-756, Republic of Korea.
authors.forename: Mei Jing
authors.initials: MJ
authors.lastname: Piao
authors.affiliation: School of Medicine, Jeju National University, Jeju 690-756, Republic of Korea.
authors.forename: Susara Ruwan Kumara Madduma
authors.initials: SR
authors.lastname: Hewage
authors.affiliation: School of Medicine, Jeju National University, Jeju 690-756, Republic of Korea.
authors.forename: Chang Lim
authors.initials: CL
authors.lastname: Hyun
authors.affiliation: School of Medicine, Jeju National University, Jeju 690-756, Republic of Korea. Electronic address: sukjucho@gmail.com.
authors.forename: Suk Ju
authors.initials: SJ
authors.lastname: Cho
authors.affiliation: School of Medicine, Jeju National University, Jeju 690-756, Republic of Korea. Electronic address: jinwonh@jejunu.ac.kr.
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Hyun
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism*; D053938:DNA Fragmentation; D019073:HT29 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014468:Umbelliferones / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D014468:Umbelliferones; D020928:Mitogen-Activated Protein Kinases; D053148:Caspase 3; D053453:Caspase 9; C007628:esculetin
keywords: Apoptosis; Esculetin; Human colon cancer; Reactive oxygen species; Signal pathway