Maesopsin 4-O-β-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

• Published in: Journal of chemotherapy (Florence) 2011-06, Vol.23 (3), p.150-157
• Main Authors: Pozzesi, N., Pierangeli, S., Vacca, C., Falchi, L., Pettorossi, V., Martelli, M.P., Thuy, T.T., Ninh, P.T., Liberati, A.M., Riccardi, C., Sung, T.V., Delfino, D.V.
• Format: Article
• Language: English
• Subjects: acute myeloid leukemia; Antibiotics. Antiinfectious agents. Antiparasitic agents; Artocarpus - chemistry; Artocarpus tonkinensis; BCAS3; Benzofurans - pharmacology; Biological and medical sciences; 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; Hematologic and hematopoietic diseases; Heme Oxygenase-1 - biosynthesis; Heme Oxygenase-1 - genetics; HL-60 Cells; HMOX1; 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; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; maesopsin 4-O-β-D-glucoside; Male; Medical sciences; 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; Pharmacology. Drug treatments; proliferation; SRXN1; T-Lymphocytes - drug effects; Transcription Factors - genetics; Transforming Growth Factor beta - metabolism; U937 Cells; Up-Regulation - drug effects
• ISSN: 1120-009X; 1973-9478
• DOI: 10.1179/joc.2011.23.3.150

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.