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Text Box: F3





Evid Based Complement Alternat Med. 2009 Aug 20. [Epub ahead of print]

Ganoderma lucidum Polysaccharides Induce Macrophage-like Differentiation in Human Leukemia THP-1 Cells via Caspase and p53 Activation.

Hsu JW, Huang HC, Chen ST, Wong CH, Juan HF.

Department of Life Science, Institute of Molecular and Cellular Biology, National Taiwan University, No 1, Sec. 4, Roosevelt Road, Taipei, 106 Taiwan. yukijuan@ntu.edu.tw, yukijuan@gmail.com.

Differentiation therapy by induction of tumor cells is an important method in the treatment of hematological cancers such as leukemia. Tumor cell differentiation ends cancer cells' immortality, thus stopping cell growth and proliferation. In our previous study, we found that fucose-containing polysaccharide fraction F3 extracted from Ganoderma lucidum can bring about cytokine secretion and cell death in human leukemia THP-1 cells. This prompted us to further investigate on how F3 induces the differentiation in human leukemia cells. We integrated time-course microarray analysis and network modeling to study the F3-induced effects on THP-1 cells. In addition, we determined the differentiation effect using Liu's staining, nitroblue tetrazolium (NBT) reduction assay, flow cytometer, western blotting and Q-PCR. We also examined the modulation and regulation by F3 during the differentiation process. Dynamic gene expression profiles showed that cell differentiation was induced in F3-treated THP-1 cells. Furthermore, F3-treated THP-1 cells exhibited enhanced macrophage differentiation, as demonstrated by changes in cell adherence, cell cycle arrest, NBT reduction and expression of differentiation markers including CD11b, CD14, CD68, matrix metalloproteinase-9 and myeloperoxidase. In addition, caspase cleavage and p53 activation were found to be significantly enhanced in F3-treated THP-1 cells. We unraveled the role of caspases and p53 in F3-induced THP-1 cells differentiation into macrophages. Our results provide a molecular explanation for the differentiation effect of F3 on human leukemia THP-1 cells and offer a prospect for a potential leukemia differentiation therapy.

PMID: 19696196 [PubMed - as supplied by publisher

Clin Chem.2009 Oct;55(10):1834-42. Epub 2009 Aug 6.

Increased tissue factorexpression is associated with reduced survival in non-small cell lungcancer and with mutations of TP53 and PTEN.

Regina S,Valentin JB,Lachot S,LemariéE,Rollin J,Gruel Y.

Department ofHematology-Hemostasis, Trousseau Hospital and François Rabelais University,Tours, France.

BACKGROUND: Tissue factor(TF), the main initiator of blood coagulation, is also a signaling proteinthat regulates cancer progression. TF synthesis was recently shown to beaffected by tumor suppressor genes (TSGs) in tumor cell lines. We thereforestudied TF gene (F3) expression and the status of genes coding for tumorprotein p53 (TP53), phosphatase and tensin homolog (PTEN), andserine/threonine kinase 11 (STK11) in non-small cell lung cancer (NSCLC).Heparanase (HPSE) gene expression was also measured because thisendo-beta-D-glucuronidase was recently shown to enhance TF gene expression.METHODS: TF and heparanase mRNA expression was measured by real-time PCR in53 NSCLC tumors. Exons 5-8 of TP53 were sequenced from genomic DNA.Mutations of PTEN and STK11 were screened by multiplex ligation-dependentprobe amplification. RESULTS: TF mRNA levels were significantly higher inT(3)-T(4) tumors (P = 0.04) and in stages III-IV of NSCLC (P = 0.03).Mutations of TP53, STK11, and PTEN were identified in 20 (37.7%), 21 (39%),and 20 (37.7%) of tumors, respectively. TF expression was higher in mutatedTP53 (TP53(Mut)) (P = 0.02) and PTEN(Mut) (P = 0.03) samples. Moreover, TFmRNA increased from 2700 copies (no mutation) to 11 6415 when 3 TSG weremutated. Heparanase gene expression did not differ according to TF gene(F3) expression or TSG mutation. The median survival time was shorter inpatients with tumor TF mRNA levels above median values (relative risk 2.2;P = 0.03, multivariate analysis) and when TP53 was mutated (relative risk1.8; P = 0.02). CONCLUSIONS: These results provide clear evidence thatcombined oncogene events affecting TSG dramatically increase TF geneexpression in lung tumors. Moreover, this study suggests that TF geneexpression could be used as a prognostic marker in NSCLC.

PMID: 19661141 [PubMed