Curcumin inhibitsin vitroandin vivochronic 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.

Identification of suitable reference gene and biomarkers of serum miRNAs for osteoporosis

“…Finally, it maybe resulted from the selective package and secretion process of circulating miRNA. Previous reports showed that the expression pattern of some miRNAs in intracellular was contrary to that in extracellular owing to the selective disposal363738.…”

WITHDRAWN: Expression profiles and biological implications of plasma miRNAs associated with chronic myeloid leukemia phases

“…Patients with a low plasma miR-215 expression had a significantly higher total imatinib intake compared to patients with increased miR-215 expression [13]. miR-21 was enriched in exosomes released by K562 and LAMA84 cells after treatment with curcumin, suggesting that selective packaging of miR-21 in the exosomes may contribute to the antileukemic effect of curcumin in CML [14].…”

Natural Compounds: Molecular Weapons against Leukemia’s

“…Curcumin also induced the up-regulation of miR-196b and a decrease of BCR-ABL at mRNA and protein level. For these reasons, curcumin can be considered a promising compound that in association with conventional tyrosine kinase inhibitor, may improve the therapeutic approach for CML patients resistant to Imatinib [21]. Moreover, exosomes containing miR-21 and released by CML cells treated with curcumin were able to modulate the endothelial barrier organization and attenuated the angiogenic phenotype.…”