title: Curcumin inhibits in vitro and in vivo chronic myelogenous leukemia cells growth: a possible role for exosomal disposal of miR-21.
abstract: Exosomes are nanosize vesicles released from cancer cells containing microRNAs that can influence gene expression in target cells. Curcumin has been shown to exhibit antitumor activities in a wide spectrum of human cancer. The addition of Curcumin, to Chronic Myelogenous Leukemia (CML) cells, caused a dose-dependent increase of PTEN, target of miR-21. Curcumin treatment also decreased AKT phosphorylation and VEGF expression and release. Colony formation assays indicated that Curcumin affects the survival of CML cells. Some observation suggest a possible cellular disposal of miRNAs by exosomes. To elucidate if Curcumin caused a decrease of miR-21 in CML cells and its packaging in exosomes, we analyzed miR-21 content in K562 and LAMA84 cells and exosomes, after treatment with Curcumin. Furthermore, we showed that addition of Curcumin to CML cells caused a downregulation of Bcr-Abl expression through the cellular increase of miR-196b.The effects of Curcumin was then investigated on a CML xenograft in SCID mice. We observed that animals treated with Curcumin, developed smaller tumors compared to mice control. Real time PCR analysis showed that exosomes, released in the plasma of the Curcumin-treated mice, were enriched in miR-21 with respect control. Taken together, our results suggested that a selective packaging of miR-21 in exosomes may contribute to the antileukemic effect of Curcumin in CML.
authors.affiliation: Dipartimento di Biopatologia e Metodologie Biomediche, Sezione di Biologia e Genetica, Università di Palermo, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Taverna
authors.affiliation: Dipartimento di Biopatologia e Metodologie Biomediche, Sezione di Biologia e Genetica, Università di Palermo, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Giallombardo
authors.affiliation: Dipartimento di Biopatologia e Metodologie Biomediche, Sezione di Biologia e Genetica, Università di Palermo, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Pucci
authors.affiliation: Dipartimento di Biopatologia e Metodologie Biomediche, Sezione di Biologia e Genetica, Università di Palermo, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Flugy
authors.affiliation: Istituto di Biofisica, CNR, Palermo, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Manno
authors.affiliation: Istituto di Biofisica, CNR, Palermo, Italy.
authors.forename: Samuele
authors.initials: S
authors.lastname: Raccosta
authors.affiliation: Phase I - Early Clinical Trials Unit Oncology Department and Center of Oncological Research (CORE), University Hospital Antwerp & Antwerp University, Belgium.
authors.forename: Christian
authors.initials: C
authors.lastname: Rolfo
authors.affiliation: Dipartimento di Biopatologia e Metodologie Biomediche, Sezione di Biologia e Genetica, Università di Palermo, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: De Leo
authors.affiliation: Dipartimento di Biopatologia e Metodologie Biomediche, Sezione di Biologia e Genetica, Università di Palermo, Italy.|Istituto di Biomedicina e Immunologia Molecolare (IBIM), Consiglio Nazionale delle Ricerche, Palermo, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Alessandro
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D055354:Exosomes / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D011897:Random Allocation; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D003474:Curcumin
keywords: CML; Curcumin; exosomes; miR-21; microRNAs