Inhibitory effects of costunolide on the telomerase activity in human breast carcinoma cells

Sang-Ho Choi; Eunok Im; Hyun Kyung Kang; Ji-Hyeon Lee; Hi-Suk Kwak; Young-Tae Bae; Hee-Juhn Park; Nam Deuk Kim

doi:10.1016/j.canlet.2005.01.011

Inhibitory effects of costunolide on the telomerase activity in human breast carcinoma cells

Cancer Lett. 2005 Sep 28;227(2):153-62. doi: 10.1016/j.canlet.2005.01.011.

Authors

Sang-Ho Choi¹, Eunok Im, Hyun Kyung Kang, Ji-Hyeon Lee, Hi-Suk Kwak, Young-Tae Bae, Hee-Juhn Park, Nam Deuk Kim

Affiliation

¹ Department of Pharmacy, College of Pharmacy, and Research Institute for Drug Development, Pusan National University, Busan 609-735, South Korea.

PMID: 16112418
DOI: 10.1016/j.canlet.2005.01.011

Abstract

Costunolide, a natural sesquiterpene compound, has been known having cytotoxic and chemopreventive effects on various human cancer cells. In the present study, we examined the effects of costunolide on telomerase activity and on the components of telomerase in MCF-7 (wild-type p53) and MDA-MB-231 (mutant p53) cells. We found that costunolide inhibited the growth and telomerase activity of MCF-7 and MDA-MB-231 cells in a concentration- and time-dependent manner. The expression of hTERT mRNA was also inhibited but hTR mRNA was not. In addition, the bindings of transcription factors in hTERT promoters were significantly decreased in both cells by the treatment of costunolide. These results suggest that costunolide inhibited the growth of both MCF-7 and MDA-MB-231 cells and this effect was mediated at least in part by a significant reduction in telomerase activity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents, Phytogenic / pharmacology*
Breast Neoplasms / enzymology
Breast Neoplasms / pathology*
DNA, Neoplasm / genetics
DNA, Neoplasm / metabolism
DNA-Binding Proteins / drug effects
DNA-Binding Proteins / metabolism*
Female
Humans
Nitric Oxide Synthase / antagonists & inhibitors
Promoter Regions, Genetic / genetics
Proto-Oncogene Proteins c-myb / metabolism
RNA / metabolism*
RNA, Messenger / metabolism
RNA, Neoplasm / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Sesquiterpenes / pharmacology*
Sp1 Transcription Factor / metabolism
Sp3 Transcription Factor
Telomerase / drug effects
Telomerase / metabolism*
Transcription Factors / metabolism
Tumor Cells, Cultured
Tumor Suppressor Protein p53 / genetics

Substances

Antineoplastic Agents, Phytogenic
DNA, Neoplasm
DNA-Binding Proteins
Proto-Oncogene Proteins c-myb
RNA, Messenger
RNA, Neoplasm
Sesquiterpenes
Sp1 Transcription Factor
Transcription Factors
Tumor Suppressor Protein p53
telomerase RNA
Sp3 Transcription Factor
costunolide
RNA
Nitric Oxide Synthase
Telomerase