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Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo 170-8455 [H. S., T. O-h., I. N., T. T.]; Chemical Synthesis Laboratory [T. Su., K. T.],and Life Science Laboratory Mitsui Chemicals, Inc., Chiba 297-0017; and Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo 113-0032 [I. N., T. T.], Japan

Epidemiological studies suggest potent anticancer effects of tea catechins. Previously, we have reported (I. Naasani et al., Biochem. Biophys. Res. Commun., 249: 391–396, 1998) that epigallocatechin gallate (EGCG), a major tea catechin, strongly and directly inhibits telomerase, a ribonucleoprotein that maintains telomeres and has been implicated in tumorigenesis. Here, we describe newly synthesized compounds MST-312, MST-295, and MST-199, as more effective telomerase inhibitors than EGCG. Continuous treatment of human monoblastoid leukemia U937 cells with a nontoxic dose of each drug caused progressive telomere shortening and eventual reduction of growth rate accompanied by induction of the senescence-associated ß-galactosidase activity. Particularly, in the case of MST-312, the effective dose required for the telomere shortening was 1–2 µM, which was 15- to 20-fold lower than that of EGCG. These compounds may provide a novel chemotherapeutic strategy for the treatment of cancers.

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