Maesopsin 4-O-beta-D-glucoside, a natural compound isolated from the leaves of Artocarpus tonkinensis, inhibits proliferation and up-regulates HMOX1, SRXN1 and BCAS3 in acute myeloid leukemia

N Pozzesi; S Pierangeli; Carmine Vacca; L Falchi; V Pettorossi; M P Martelli; T T Thuy; P T Ninh; A M Liberati; C Riccardi; T V Sung; D V Delfino

doi:10.1179/joc.2011.23.3.150

Maesopsin 4-O-beta-D-glucoside, a natural compound isolated from the leaves of Artocarpus tonkinensis, inhibits proliferation and up-regulates HMOX1, SRXN1 and BCAS3 in acute myeloid leukemia

J Chemother. 2011 Jun;23(3):150-7. doi: 10.1179/joc.2011.23.3.150.

Authors

N Pozzesi¹, S Pierangeli, Carmine Vacca, L Falchi, V Pettorossi, M P Martelli, T T Thuy, P T Ninh, A M Liberati, C Riccardi, T V Sung, D V Delfino

Affiliation

¹ Section of Pharmacology, Toxicology and Chemotherapy, Department of Clinical and Experimental Medicine, University of Perugia, Via del Giochetto, Perugia, Italy.

PMID: 21742584
DOI: 10.1179/joc.2011.23.3.150

Abstract

The leaves of Artocarpus tonkinensis are used in Vietnamese traditional medicine for treatment of arthritis, and the compound maesopsin 4-O-β-D-glucoside (TAT-2), isolated from them, inhibits the proliferation of activated T cells. Our goal was to test the anti-proliferative activity of TAT-2 on the T-cell leukemia, Jurkat, and on the acute myeloid leukemia, OCI-AML. TAT-2 inhibited the growth of OCI-AML (and additional acute myeloid leukemia cells) but not Jurkat cells. Growth inhibition was shown to be due to inhibition of proliferation rather than increase in cell death. Analysis of cytokine release showed that TAT-2 stimulated the release of TGF-β, yet TGF-β neutralization did not reverse the maesopsin-dependent effect. Gene expression profiling determined that maesopsin modulated 19 identifiable genes. Transcription factor CP2 was the gene most significantly modulated. Real-time PCR validated that up-regulation of sulphiredoxin 1 homolog (SRXN1), hemeoxygenase 1 (HMOX1), and breast carcinoma amplified sequence 3 (BCAS3) were consistently modulated.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Artocarpus / chemistry
Benzofurans / pharmacology*
Cell Death / drug effects
Cell Growth Processes / drug effects
Cell Line, Tumor
DNA-Binding Proteins / genetics
Dose-Response Relationship, Drug
Gene Expression / drug effects
Gene Expression Profiling / methods
Glucosides / pharmacology*
HL-60 Cells
Heme Oxygenase-1 / biosynthesis
Heme Oxygenase-1 / genetics*
Humans
Jurkat Cells
Leukemia, Myeloid, Acute / drug therapy*
Leukemia, Myeloid, Acute / genetics*
Leukemia, Myeloid, Acute / metabolism
Leukemia, Myeloid, Acute / pathology
Leukemia, T-Cell / drug therapy
Leukemia, T-Cell / genetics
Leukemia, T-Cell / metabolism
Leukemia, T-Cell / pathology
Male
Middle Aged
Neoplasm Proteins / biosynthesis
Neoplasm Proteins / genetics*
Oligonucleotide Array Sequence Analysis / methods
Oxidoreductases Acting on Sulfur Group Donors / biosynthesis
Oxidoreductases Acting on Sulfur Group Donors / genetics*
T-Lymphocytes / drug effects
Transcription Factors / genetics
Transforming Growth Factor beta / metabolism
U937 Cells
Up-Regulation / drug effects

Substances

BCAS3 protein, human
Benzofurans
DNA-Binding Proteins
Glucosides
Neoplasm Proteins
TFCP2 protein, human
Transcription Factors
Transforming Growth Factor beta
maesopsin 4-O-glucoside
HMOX1 protein, human
Heme Oxygenase-1
Oxidoreductases Acting on Sulfur Group Donors
SRXN1 protein, human