title: A synthesized nostocionone derivative potentiates programmed cell death in human T-cell leukemia Jurkat cells through mitochondria via the release of endonuclease G.
abstract: Nostocionone (Nost), a compound isolated from Nostoc commune, and its synthesized derivatives (NostDs) were evaluated for in vitro cytotoxicity against human T-cell leukemia Jurkat cells. NostD3 [(1E,4E)-1-(3,4-dihydroxyphenyl)-5-(2,6,6-trimethylcyclohex-1-enyl)penta-1,4-dien-3-one] inhibited cell growth more potently than Nost. To elucidate the mechanisms of NostD3-induced cell death, we examined changes in cell morphology, the loss of mitochondrial membrane potential (MMT), and DNA fragmentation. From these results, the cytotoxic effects of NostD3 were found to be mainly due to Type I programmed cell death (PCDI; i.e., apoptosis). Using caspase inhibitors, we further found that NostD-3-induced PCDI occurred through a caspase-independent pathway. Moreover, NostD3 decreased MMT and modulated multiple signaling molecules (MAPKs, Akt, Bcl-2, Bax, and c-Myc) in Jurkat cells, thereby inducing the release of endonuclease G (Endo-G) from mitochondria. The level of intracellular reactive oxygen species (ROS) in cells treated with NostD3 was elevated up to 1 h after the treatment. However, suppression of ROS by N-acetyl-l-cysteine restored Jurkat cell growth. Taken together, our data suggested that ROS production acted as a trigger in NostD3-induced PCDI in Jurkat cells through release of Endo-G from the mitochondria.
authors.affiliation: a Laboratory of Aquatic Food Science, Department of Fisheries, Faculty of Agriculture , Kinki University , Nara , Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Itoh
authors.forename: Yuji
authors.initials: Y
authors.lastname: Muramatsu
authors.forename: Masayo
authors.initials: M
authors.lastname: Masu
authors.forename: Ayaka
authors.initials: A
authors.lastname: Tsuge
authors.forename: Masaki
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ninomiya
authors.forename: Masashi
authors.initials: M
authors.lastname: Ando
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Tsukamasa
authors.forename: Mamoru
authors.initials: M
authors.lastname: Koketsu
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects*; D004706:Endodeoxyribonucleases / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D007938:Leukemia / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D050501:Nostoc commune / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D004706:Endodeoxyribonucleases; C052391:endonuclease G; D000111:Acetylcysteine