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Enhancement of adriamycin cytotoxicity by sodium butyrate involves hTERT downmodulation-mediated apoptosis in human uterine cancer cells.

Abstract
Activation of telomerase is a key element in oncogenesis and resistance to apoptosis for many cancers. Some histone deacetylase inhibitors (HDACi) or chemotheraputic agents have been reported to downregulate the expression of human telomerase reverse transcriptase (hTERT). However, whether hTERT is involved in cell death of uterine cancer cells induced by combination of HDACi with chemotheraputic regents remain unknown. The present study shows that combining sodium butyrate (NaBu) and adriamycin (ADR) inhibits proliferation of uterine cancer cell lines in a concentration and time-dependent manner. Growth inhibition was accompanied by caspase-dependent apoptosis with reduced telomerase activity and decreased hTERT mRNA expression. Ectopic wild type (WT)-hTERT suppressed the apoptosis induced by NaBu/ADR treatment, while knockdown of hTERT sensitized uterine cancer cells to ADR. Moreover, the addition of NaBu significantly enhanced ADR cytotoxicity for the primary uterine cancer cells with high hTERT expression. These data indicate that downregulation of hTERT is an important part of the mechanism by which NaBu enhances ADR-induced apoptosis, and suggests that combining NaBu and ADR may be effective in treating uterine tumor with high telomerase activity.
AuthorsMeng Yu, Hong Kong, Yan Zhao, Xuefei Sun, Zhihong Zheng, Chunming Yang, Yuyan Zhu
JournalMolecular carcinogenesis (Mol Carcinog) Vol. 53 Issue 7 Pg. 505-13 (Jul 2014) ISSN: 1098-2744 [Electronic] United States
PMID23359532 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2013 Wiley Periodicals, Inc.
Chemical References
  • Antibiotics, Antineoplastic
  • Histamine Antagonists
  • Histone Deacetylase Inhibitors
  • RNA, Messenger
  • RNA, Small Interfering
  • Butyric Acid
  • Doxorubicin
  • TERT protein, human
  • Telomerase
  • Caspase 8
  • Caspase 9
Topics
  • Antibiotics, Antineoplastic (pharmacology)
  • Apoptosis (drug effects)
  • Butyric Acid (pharmacology)
  • Caspase 8 (genetics, metabolism)
  • Caspase 9 (genetics, metabolism)
  • Cell Line, Tumor
  • Cell Proliferation (drug effects)
  • Down-Regulation
  • Doxorubicin (pharmacology)
  • Drug Synergism
  • Endometrial Neoplasms (enzymology)
  • Enzyme Activation
  • Female
  • HeLa Cells
  • Histamine Antagonists (pharmacology)
  • Histone Deacetylase Inhibitors (pharmacology)
  • Humans
  • RNA Interference
  • RNA, Messenger (biosynthesis)
  • RNA, Small Interfering (genetics)
  • Telomerase (biosynthesis, genetics)

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