Low-Dose Uroacitides(CDA-II) Downregulates Telomerase Activity and Inhibits Proliferation in the Telomerase-Expressing Maliganant Cell Lines Through Inactivation of Akt Signaling Pathway

Abstract 4920

Uroacitides, another name CDA-II (cell differentiation agent II), is a mixture product and isolated from healthy human urine in China. It is characterized as a novel molecular targeting agent for cancer therapy. Multiple active components, such as peptides (MW 400–2800), organic acids, pigments and phenylacetylglutamine, with different mechanisms of action act concurrently to contribute to the anticancer effect of CDA-II. We have reported that high-dose CDA-II could induce acute myeloid leukemia (AML) cell apoptosis. Here, in the light of the important role of telomerase in malignant transformation. We evaluated the effect of low-dose CDA-II on telomerase activity (TA) and regulation in various malignant cell lines. CDA-II caused a dose-dependent inhibition of TA (up to 80% at a concentration of 0. 5 mg/mL) in Hela (cervix uteri cancer), MCF-7(breast cancer), SW480(colon cancer), RPMI8226(myeloma), HL-60 (AML), Raji (Burkitt lymphoma), L428 (Hodgkin's disease). Low-dose CDA-II did not affect the activity of other DNA polymerases. Inhibition of TA was associated with 60% inhibition of proliferation. The inhibition of proliferation was associated with a decrease in the S phase of the cell cycle and an accumulate of cells in G1 phase. No apoptosis was observed. Inhibition of TA was caused by dephosphorylation of Akt and by early downregulation of hTERT transcription. Other steps of telomerase regulation were not affected by low-dose CDA-II. This study demonstrated an additional cellular target of low-dose CDA-II that causes inhibition of TA and cell proliferation.