Mitochondria are the target organelle of differentiation-inducing factor-3, an anti-tumor agent isolated from Dictyostelium discoideum [corrected].

Differentiation-inducing factor-3 (DIF-3), found in the cellular slime mold Dictyostelium discoideum, and its derivatives such as butoxy-DIF-3 (Bu-DIF-3) are potent anti-tumor agents. However, the precise mechanisms underlying the actions of DIF-3 remain to be elucidated. In this study, we synthesiz...

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Autores principales:	Yuzuru Kubohara, Haruhisa Kikuchi, Yusuke Matsuo, Yoshiteru Oshima, Yoshimi Homma
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9528ad06b63348e8840d5b19a0620b78
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spelling	oai:doaj.org-article:9528ad06b63348e8840d5b19a0620b782021-11-18T08:59:24ZMitochondria are the target organelle of differentiation-inducing factor-3, an anti-tumor agent isolated from Dictyostelium discoideum [corrected].1932-620310.1371/journal.pone.0072118https://doaj.org/article/9528ad06b63348e8840d5b19a0620b782013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23977224/?tool=EBIhttps://doaj.org/toc/1932-6203Differentiation-inducing factor-3 (DIF-3), found in the cellular slime mold Dictyostelium discoideum, and its derivatives such as butoxy-DIF-3 (Bu-DIF-3) are potent anti-tumor agents. However, the precise mechanisms underlying the actions of DIF-3 remain to be elucidated. In this study, we synthesized a green fluorescent derivative of DIF-3, BODIPY-DIF-3, and a control fluorescent compound, Bu-BODIPY (butyl-BODIPY), and investigated how DIF-like molecules behave in human cervical cancer HeLa cells by using both fluorescence and electron microscopy. BODIPY-DIF-3 at 5-20 µ M suppressed cell growth in a dose-dependent manner, whereas Bu-BODIPY had minimal effect on cell growth. When cells were incubated with BODIPY-DIF-3 at 20 µM, it penetrated cell membranes within 0.5 h and localized mainly in mitochondria, while Bu-BODIPY did not stain the cells. Exposure of cells for 1-3 days to DIF-3, Bu-DIF-3, BODIPY-DIF-3, or CCCP (a mitochondrial uncoupler) induced substantial mitochondrial swelling, suppressing cell growth. When added to isolated mitochondria, DIF-3, Bu-DIF-3, and BOIDPY-DIF-3, like CCCP, dose-dependently promoted the rate of oxygen consumption, but Bu-BODIPY did not. Our results suggest that these bioactive DIF-like molecules suppress cell growth, at least in part, by disturbing mitochondrial activity. This is the first report showing the cellular localization and behavior of DIF-like molecules in mammalian tumor cells.Yuzuru KuboharaHaruhisa KikuchiYusuke MatsuoYoshiteru OshimaYoshimi HommaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 8, p e72118 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yuzuru Kubohara Haruhisa Kikuchi Yusuke Matsuo Yoshiteru Oshima Yoshimi Homma Mitochondria are the target organelle of differentiation-inducing factor-3, an anti-tumor agent isolated from Dictyostelium discoideum [corrected].
description	Differentiation-inducing factor-3 (DIF-3), found in the cellular slime mold Dictyostelium discoideum, and its derivatives such as butoxy-DIF-3 (Bu-DIF-3) are potent anti-tumor agents. However, the precise mechanisms underlying the actions of DIF-3 remain to be elucidated. In this study, we synthesized a green fluorescent derivative of DIF-3, BODIPY-DIF-3, and a control fluorescent compound, Bu-BODIPY (butyl-BODIPY), and investigated how DIF-like molecules behave in human cervical cancer HeLa cells by using both fluorescence and electron microscopy. BODIPY-DIF-3 at 5-20 µ M suppressed cell growth in a dose-dependent manner, whereas Bu-BODIPY had minimal effect on cell growth. When cells were incubated with BODIPY-DIF-3 at 20 µM, it penetrated cell membranes within 0.5 h and localized mainly in mitochondria, while Bu-BODIPY did not stain the cells. Exposure of cells for 1-3 days to DIF-3, Bu-DIF-3, BODIPY-DIF-3, or CCCP (a mitochondrial uncoupler) induced substantial mitochondrial swelling, suppressing cell growth. When added to isolated mitochondria, DIF-3, Bu-DIF-3, and BOIDPY-DIF-3, like CCCP, dose-dependently promoted the rate of oxygen consumption, but Bu-BODIPY did not. Our results suggest that these bioactive DIF-like molecules suppress cell growth, at least in part, by disturbing mitochondrial activity. This is the first report showing the cellular localization and behavior of DIF-like molecules in mammalian tumor cells.
format	article
author	Yuzuru Kubohara Haruhisa Kikuchi Yusuke Matsuo Yoshiteru Oshima Yoshimi Homma
author_facet	Yuzuru Kubohara Haruhisa Kikuchi Yusuke Matsuo Yoshiteru Oshima Yoshimi Homma
author_sort	Yuzuru Kubohara
title	Mitochondria are the target organelle of differentiation-inducing factor-3, an anti-tumor agent isolated from Dictyostelium discoideum [corrected].
title_short	Mitochondria are the target organelle of differentiation-inducing factor-3, an anti-tumor agent isolated from Dictyostelium discoideum [corrected].
title_full	Mitochondria are the target organelle of differentiation-inducing factor-3, an anti-tumor agent isolated from Dictyostelium discoideum [corrected].
title_fullStr	Mitochondria are the target organelle of differentiation-inducing factor-3, an anti-tumor agent isolated from Dictyostelium discoideum [corrected].
title_full_unstemmed	Mitochondria are the target organelle of differentiation-inducing factor-3, an anti-tumor agent isolated from Dictyostelium discoideum [corrected].
title_sort	mitochondria are the target organelle of differentiation-inducing factor-3, an anti-tumor agent isolated from dictyostelium discoideum [corrected].
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/9528ad06b63348e8840d5b19a0620b78
work_keys_str_mv	AT yuzurukubohara mitochondriaarethetargetorganelleofdifferentiationinducingfactor3anantitumoragentisolatedfromdictyosteliumdiscoideumcorrected AT haruhisakikuchi mitochondriaarethetargetorganelleofdifferentiationinducingfactor3anantitumoragentisolatedfromdictyosteliumdiscoideumcorrected AT yusukematsuo mitochondriaarethetargetorganelleofdifferentiationinducingfactor3anantitumoragentisolatedfromdictyosteliumdiscoideumcorrected AT yoshiteruoshima mitochondriaarethetargetorganelleofdifferentiationinducingfactor3anantitumoragentisolatedfromdictyosteliumdiscoideumcorrected AT yoshimihomma mitochondriaarethetargetorganelleofdifferentiationinducingfactor3anantitumoragentisolatedfromdictyosteliumdiscoideumcorrected
_version_	1718421097688334336

Mitochondria are the target organelle of differentiation-inducing factor-3, an anti-tumor agent isolated from Dictyostelium discoideum [corrected].

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