Novel semisynthetic triterpenoid AMR-Me inhibits telomerase activity in human leukemic CEM cells and exhibits in vivo antitumor activity against Dalton's lymphoma ascites tumor.

Thangaiyan Rabi, Sipra Banerjee

Department of Cancer Biology, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA. trabi@uri.edu

Cancer letters 2009 Jun 18

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Telomerase, a ribonucleoprotein complex of hTERT and hTER, has been reported to be associated with carcinogenesis and multidrug resistance (MDR). Methyl-25-hydroxy-3-oxoolean-12-en-28-oate (AMR-Me) is a novel semisynthetic triterpenoid, derived from a triterpene acid isolated from the stem bark of a tropical tree Amoora rohituka grown wild in India. We examined the role of telomerase in mediating the growth suppression of human acute lymphoblastic leukemic CEM cells by AMR-Me. The results showed that AMR-Me inhibited the growth and viability of CEM cells, induced apoptosis and cell cycle arrest in G(2)+M phase. AMR-Me treatment resulted in suppression of hTERT expression and a concomitant inhibition of telomerase activity. The in vivo antitumor activity of AMR-Me was determined using mice inoculated with Dalton's lymphoma ascites tumor cells. Intraperitoneal administration of the AMR-Me at doses of 1 or 3mg/kg, increased the survival rate by 121% and 133% respectively, without weight change over the treatment period. Our results suggest that AMR-Me inhibits telomerase activity by decreasing the hTERT expression and induces apoptosis in human lymphoblastic leukemic CEM cells, thus providing the molecular basis for the development of AMR-Me as a novel chemotherapeutic agent against leukemia.

Citation

Thangaiyan Rabi, Sipra Banerjee. Novel semisynthetic triterpenoid AMR-Me inhibits telomerase activity in human leukemic CEM cells and exhibits in vivo antitumor activity against Dalton's lymphoma ascites tumor. Cancer letters. 2009 Jun 18;278(2):156-63