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.

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.

• Authors: 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
• Journal: Journal of chemotherapy (Florence, Italy) (J Chemother) Vol. 23 Issue 3 Pg. 150-7 (06 2011) ISSN: 1973-9478 [Electronic] England
• PMID: 21742584 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

• 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, genetics)
• Humans
• Jurkat Cells
• Leukemia, Myeloid, Acute (drug therapy, genetics, metabolism, pathology)
• Leukemia, T-Cell (drug therapy, genetics, metabolism, pathology)
• Male
• Middle Aged
• Neoplasm Proteins (biosynthesis, genetics)
• Oligonucleotide Array Sequence Analysis (methods)
• Oxidoreductases Acting on Sulfur Group Donors (biosynthesis, genetics)
• T-Lymphocytes (drug effects)
• Transcription Factors (genetics)
• Transforming Growth Factor beta (metabolism)
• U937 Cells
• Up-Regulation (drug effects)