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Abstract Title:

P53-dependent downregulation of hTERT protein expression and telomerase activity induces senescence in lung cancer cells as a result of pterostilbene treatment.

Abstract Source:

Cell Death Dis. 2017 Aug 10 ;8(8):e2985. Epub 2017 Aug 10. PMID: 28796247

Abstract Author(s):

Rong-Jane Chen, Pei-Hsuan Wu, Chi-Tang Ho, Tzong-Der Way, Min-Hsiung Pan, Hsiu-Min Chen, Yuan-Soon Ho, Ying-Jan Wang

Article Affiliation:

Rong-Jane Chen

Abstract:

Cellular senescence is characterized by permanent cell cycle arrest, triggered by a variety of stresses, such as telomerase inhibition, and it is recognized as a tumor-suppressor mechanism. In recent years, telomerase has become an important therapeutic target in several cancers; inhibition of telomerase can induce senescence via the DNA damage response (DDR). Pterostilbene (PT), a dimethyl ether analog of resveratrol, possesses a variety of biological functions, including anticancer effects; however, the molecular mechanisms underlying these effects are not fully understood. In this study, we investigated the possible mechanisms of PT-induced senescence through telomerase inhibition in human non-small cell lung cancer cells and delineated the role of p53 in senescence. The results indicated that PT-induced senescence is characterized by a flattened morphology, positive staining for senescence-associated-β galactosidase activity, and the formation of senescence-associated heterochromatic foci. Telomerase activity and protein expression was significantly decreased in H460 (p53 wild type) cells compared with H1299 (p53 null) cells and p53 knockdown H460 cells (H460-p53-). A more detailed mechanisticstudy revealed that PT-induced senescence partially occurred via a p53-dependent mechanism, triggering inhibition of telomerase activity and protein expression, and leading to the DDR, S phase arrest and, finally, cellular senescence. This study is the first to explore the novel anticancer mechanismof PT senescence induction via the inhibition of telomerase in lung cancer cells.

Study Type : In Vitro Study

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