Pozzesi N, Pierangeli S, Vacca Carmine, Falchi L, Pettorossi V, Martelli M P, Thuy T T, Ninh P T, Liberati A M, Riccardi C, Sung T V, Delfino D V
Section of Pharmacology, Toxicology and Chemotherapy, Department of Clinical and Experimental Medicine, University of Perugia, Via del Giochetto, Perugia, Italy.
J Chemother. 2011 Jun;23(3):150-7. 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.
东京波罗蜜的叶子在越南传统医学中用于治疗关节炎,从其叶子中分离出的化合物大叶桉素4-O-β-D-葡萄糖苷(TAT-2)可抑制活化T细胞的增殖。我们的目标是测试TAT-2对T细胞白血病Jurkat细胞和急性髓细胞白血病OCI-AML细胞的抗增殖活性。TAT-2抑制OCI-AML细胞(以及其他急性髓细胞白血病细胞)的生长,但不抑制Jurkat细胞。结果表明,生长抑制是由于增殖受到抑制,而非细胞死亡增加。细胞因子释放分析表明,TAT-2刺激了TGF-β的释放,但TGF-β中和并不能逆转大叶桉素依赖性效应。基因表达谱分析确定大叶桉素可调节19个可识别的基因。转录因子CP2是受调节最显著的基因。实时PCR验证了硫氧还蛋白1同源物(SRXN1)、血红素加氧酶1(HMOX1)和乳腺癌扩增序列3(BCAS3)的上调是持续受到调节的。