Downregulation of Telomerase in CoCl2-Induced Apoptosis of Myeloid Leukemic Cells

Many reports showed that hypoxia-inducible factor-1 (HIF-1 ), the main factor activated by hypoxia, plays a role in the transcriptional regulation of the human telomerase reverse transcriptase (hTERT), one of the critical elements of the oncogenic process. As a hypoxia-mimetic agent, cobalt chloride (CoCl 2 ) can induce the accumulation of HIF-1 . Herein, we demonstrated that hTERT expression was greatly decreased during CoCl 2 -induced apoptosis in leukemic cell lines while overexpression of hTERT inhibited CoCl 2 -induced apoptosis. Knockdown of HIF-1 by shRNA in U937 cells did not abrogate CoCl 2 -induced hTERT downregulation nor CoCl 2 -induced apoptosis while inducible expression of HIF-1 decreased the expression of hTERT. Furthermore, CoCl 2 could decrease the c-myc protein in all the cells tested, no matter the HIF-1 was silenced or not. Taken together, we demonstrated that downregulation of hTERT contributes to CoCl 2 -induced apoptosis in leukemic cell lines and HIF-1 is not indispensable for CoCl 2 induced downregulation of hTERT.