Telomere shortening and growth inhibition of human cancer cells by novel synthetic telomerase inhibitors MST-312, MST-295, and MST-1991 |
| |
Authors: | Seimiya Hiroyuki Oh-hara Tomoko Suzuki Tsuneji Naasani Imad Shimazaki Toshiyuki Tsuchiya Katsutoshi Tsuruo Takashi |
| |
Affiliation: | Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo 170-8455, Japan. |
| |
Abstract: | 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 beta-galactosidase activity. Particularly, in the case of MST-312, the effective dose required for the telomere shortening was 1-2 microM, which was 15- to 20-fold lower than that of EGCG. These compounds may provide a novel chemotherapeutic strategy for the treatment of cancers. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|