title: Tianshengyuan-1 (TSY-1) regulates cellular Telomerase activity by methylation of TERT promoter.
abstract: Telomere and Telomerase have recently been explored as anti-aging and anti-cancer drug targets with only limited success. Previously we showed that the Chinese herbal medicine Tianshengyuan-1 (TSY-1), an agent used to treat bone marrow deficiency, has a profound effect on stimulating Telomerase activity in hematopoietic cells. Here, the mechanism of TSY-1 on cellular Telomerase activity was further investigated using HL60, a promyelocytic leukemia cell line, normal peripheral blood mononuclear cells, and CD34+ hematopoietic stem cells derived from umbilical cord blood. TSY-1 increases Telomerase activity in normal peripheral blood mononuclear cells and CD34+ hematopoietic stem cells with innately low Telomerase activity but decreases Telomerase activity in HL60 cells with high intrinsic Telomerase activity, both in a dose-response manner. Gene profiling analysis identified Telomerase reverse transcriptase (TERT) as the potential target gene associated with the TSY-1 effect, which was verified by both RT-PCR and western blot analysis. The β-galactosidase reporter staining assay showed that the effect of TSY-1 on Telomerase activity correlates with cell senescence. TSY-1 induced hypomethylation within TERT core promoter in HL60 cells but induced hypermethylation within TERT core promoter in normal peripheral blood mononuclear cells and CD34+ hematopoietic stem cells. TSY-1 appears to affect the Telomerase activity in different cell lines differently and the effect is associated with TERT expression, possibly via the methylation of TERT promoter.
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: Weibo
authors.initials: W
authors.lastname: Yu
authors.affiliation: Beijing Boyuantaihe Biological Technology Co., Ltd., Beijing, China.
authors.forename: Xiaotian
authors.initials: X
authors.lastname: Qin
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Beijing Boyuantaihe Biological Technology Co., Ltd., Beijing, China.
authors.forename: Yawei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Genomics Core, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Chintda
authors.initials: C
authors.lastname: Santiskulvong
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Vu
authors.affiliation: Department of Urology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.|Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Zeng
authors.affiliation: Department of Epidemiology, School of Public Health, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: Zuofeng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Chow
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.|Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: Jianyu
authors.initials: J
authors.lastname: Rao
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D018922:HL-60 Cells; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000201:enzymology; D011401:Promoter Regions, Genetic; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; C509186:TERT protein, human; D019098:Telomerase
keywords: TERT; TSY-1; Telomerase; hematopoietic cells; methylation