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  • Title: (-)-Epigallocatechin-3-gallate enhances anti-tumor effect of cytosine arabinoside on HL-60 cells.
    Author: Xu F, Zhen YS.
    Journal: Acta Pharmacol Sin; 2003 Feb; 24(2):163-8. PubMed ID: 12546725.
    Abstract:
    AIM: To study the potentiation of anti-tumor effect induced by cytosine arabinoside (AraC) with (-)-epigallocatechin-3-gallate (EGCG). METHODS: Growth curve method and MTT assay were used to measure the cytotoxic effect of AraC alone or in combination with EGCG on HL-60 cells. Flow cytometry was used to study the cell cycle distribution of HL-60 cells. Nullification assay was used to examine whether EGCG would nullify the rescue effect of deoxycytidine (dCdR) to AraC. Western blot analysis was employed to investigate bcl-2 expression. Intracellular Ca2+ assay was evaluated. RESULTS: Inhibition of HL-60 cell proliferation induced by AraC was enhanced by EGCG, with multiplication time prolonging from 48 h to 70 h and growth saturation density decreasing from 5.78 to 5.54. The MTT results indicated that IC50 was decreased from (0.34+/-0.29) micromol/L (AraC alone) to (0.11+/-0.09) micromol/L (P<0.05) (in combination with EGCG). Cell cycle analysis indicated that AraC blocked HL-60 cells in G1 phase, inhibited cells in S phase. EGCG had no effect on cell cycle at the current concentration, but enhanced the cell arrest by AraC. Nullification assay indicated that IC50 was 0.03 micromol/L (AraC alone), increased to 0.02 mmol/L when rescued with dCdR, and finally decreased to 4.8 micromol/L when addition with EGCG. The expression of bcl-2 protein was down-regulated after treatment with AraC in combination with EGCG. The intracellular Ca2+ was increased after treatment by AraC in combination with EGCG. CONCLUSION: The combination with EGCG could enhance the anti-tumor effect of AraC on HL-60 cells.
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