BACKGROUND: Telomerase activation, which is observed in most human cancers, plays an important role in carcinogenesis. Human telomerase reverse transcriptase (hTERT) is a subunit of telomerase that is essential for telomerase activity. The aim of the study was to investigate whether nonsteroidal antiinflammatory drugs (NSAIDs) inhibit telomerase activity and hTERT. METHODS: Four colon carcinoma cell lines, HT-29, COLO205, CRL-2134, and SW1116, were used in the experiments. Polymerase chain reaction-based telomeric repeat amplification (TRAP) enzyme-linked immunosorbent assay (ELISA) was used to measure telomerase activity in the cells after treatment with aspirin, indomethacin, or SC-236 (a specific cyclooxygenase-2 [COX-2] inhibitor). Expression of hTERT mRNA and protein was detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively. The dual luciferase reporter assay was performed to identify the potential cis-response elements to NSAIDs in the promoter region of hTERT. RESULTS: Aspirin, indomethacin, and SC-236 inhibited telomerase activity in HT-29, COLO205, and CRL-2134 cell lines, but not in the SW1116 cell line. NSAIDs inhibited hTERT mRNA and protein expression through suppression of hTERT transcriptional activity. The hTERT promoter fragment -145 to -330 basepairs (bp) upstream of the ATG starting site was sufficient to respond to the NSAID-induced inhibitory effect and the inhibition was COX-2-independent. CONCLUSION: NSAIDs inhibit telomerase activity at hTERT transcriptional, mRNA, and protein levels in colon carcinoma cells. The hTERT promoter fragment -145 to -330 bp may be the cis-response element to NSAIDs. (c) 2006 American Cancer Society.
BACKGROUND: Telomerase activation, which is observed in most humancancers, plays an important role in carcinogenesis. Human telomerase reverse transcriptase (hTERT) is a subunit of telomerase that is essential for telomerase activity. The aim of the study was to investigate whether nonsteroidal antiinflammatory drugs (NSAIDs) inhibit telomerase activity and hTERT. METHODS: Four colon carcinoma cell lines, HT-29, COLO205, CRL-2134, and SW1116, were used in the experiments. Polymerase chain reaction-based telomeric repeat amplification (TRAP) enzyme-linked immunosorbent assay (ELISA) was used to measure telomerase activity in the cells after treatment with aspirin, indomethacin, or SC-236 (a specific cyclooxygenase-2 [COX-2] inhibitor). Expression of hTERT mRNA and protein was detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively. The dual luciferase reporter assay was performed to identify the potential cis-response elements to NSAIDs in the promoter region of hTERT. RESULTS:Aspirin, indomethacin, and SC-236 inhibited telomerase activity in HT-29, COLO205, and CRL-2134 cell lines, but not in the SW1116 cell line. NSAIDs inhibited hTERT mRNA and protein expression through suppression of hTERT transcriptional activity. The hTERT promoter fragment -145 to -330 basepairs (bp) upstream of the ATG starting site was sufficient to respond to the NSAID-induced inhibitory effect and the inhibition was COX-2-independent. CONCLUSION: NSAIDs inhibit telomerase activity at hTERT transcriptional, mRNA, and protein levels in colon carcinoma cells. The hTERT promoter fragment -145 to -330 bp may be the cis-response element to NSAIDs. (c) 2006 American Cancer Society.
Authors: Abbas K Samadi; Alan Bilsland; Alexandros G Georgakilas; Amedeo Amedei; Amr Amin; Anupam Bishayee; Asfar S Azmi; Bal L Lokeshwar; Brendan Grue; Carolina Panis; Chandra S Boosani; Deepak Poudyal; Diana M Stafforini; Dipita Bhakta; Elena Niccolai; Gunjan Guha; H P Vasantha Rupasinghe; Hiromasa Fujii; Kanya Honoki; Kapil Mehta; Katia Aquilano; Leroy Lowe; Lorne J Hofseth; Luigi Ricciardiello; Maria Rosa Ciriolo; Neetu Singh; Richard L Whelan; Rupesh Chaturvedi; S Salman Ashraf; H M C Shantha Kumara; Somaira Nowsheen; Sulma I Mohammed; W Nicol Keith; William G Helferich; Xujuan Yang Journal: Semin Cancer Biol Date: 2015-05-05 Impact factor: 15.707
Authors: G A Doherty; S M Byrne; S C Austin; G M Scully; D M Sadlier; T G Neilan; E W Kay; F E Murray; D J Fitzgerald Journal: Br J Cancer Date: 2009-08-04 Impact factor: 7.640
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