Inhibitory effects of costunolide on the telomerase activity in human breast carcinoma cells.
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.
Choi
Sang-Ho
SH
Department of Pharmacy, College of Pharmacy, and Research Institute for Drug Development, Pusan National University, Busan 609-735, South Korea.
Im
Eunok
E
Kang
Hyun Kyung
HK
Lee
Ji-Hyeon
JH
Kwak
Hi-Suk
HS
Bae
Young-Tae
YT
Park
Hee-Juhn
HJ
Kim
Nam Deuk
ND
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology*; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011401:Promoter Regions, Genetic / Q000235:genetics; D020598:Proto-Oncogene Proteins c-myb / Q000378:metabolism; D012313:RNA / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012717:Sesquiterpenes / Q000494:pharmacology*; D016329:Sp1 Transcription Factor / Q000378:metabolism; D051705:Sp3 Transcription Factor; D019098:Telomerase / Q000187:drug effects / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D007783:Lactones
D000972:Antineoplastic Agents, Phytogenic; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D019001:Nitric Oxide Synthase; D020598:Proto-Oncogene Proteins c-myb; D012313:RNA; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D012717:Sesquiterpenes; D016329:Sp1 Transcription Factor; D051705:Sp3 Transcription Factor; D019098:Telomerase; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C422952:telomerase RNA; C002602:costunolide; D007783:Lactones