ISPO

Changes in STAT1 and ERK by water and ethanol extracts of Im-YunityTM(PSP) as mechanistic correlates of its clinical efficacy.

TC Hsieh,PhD, a X Lu,PhD b, QY Yang,PhD,c WH Chou, PhDd,JM Wu, PhDe

Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY

AIM: To investigate the mechanism of action of Im-YunityTM(PSP), a protein-bound polysaccharide mushroom extract derived from a patented Cov-1 strain, which has shown immunotherapeutic efficacy in patients diagnosed with a number of carcinomas, based on decade long studies, including double-blind phase II and III clinical trials, conducted in a large number of hospitals in China. METHODS: Human HL-60 leukemia cells were incubated with various concentrations of water and ethanol extracts of Im-YunityTM(PSP). Several cellular and biochemical parameters were measured. Changes in signal transducer and activator (STAT) family of transcription factors STAT1 were also monitored because of its reported role in cell growth arrest, and induction of apoptosis. RESULTS: Reduction of cell proliferation in treated cells was correlated with induction of apoptosis, restriction of cell cycling with an accompanying time- and dose-dependent down-regulation of the retinoblastoma proitein Rb, and suppressed expression of the p65 subunit of transcription factor NF-kB. Immuno-blot analysis of cells treated with water extract of Im-YunityTM(PSP) showed a dose- and time-dependent increase in STAT1, the magnitude of which was correlated with a reciprocal change in the expression of activated form of ERK. A less pronounced effect was seen in cells treated with ethanol extract of Im-YunityTM(PSP). CONCLUSIONS: STAT1 upregulation by Im-YunityTM(PSP) may be coordinated with derepression by ERK. A more active and highly expressed STAT1 resulting from treatment with I,'m-YunityTM(PSP) may correlate with a better clinical course in a number of cancers.

KEY WORDS: Im-YunityTM(PSP).

For more information, contact joseph_wu@nymc.edu

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Apoptosis - Molecular Mechanisms.

http://www.cancerprev.org/Journal/Issues/26/101/1092/4325