Ginger (Zingiber officinale) Extract Promotes Telomere Shortening and Induces Cellular Senescence in A549 Lung Cancer Cells
24. Oktober 2017 (online)
Cellular senescence caused by telomere shortening is considered a tumor suppressor mechanism.1 However, more than 85% of cancers maintain their telomeres by reactivating telomerase to escape the replicative senescence.2 Previously, we reported that the crude ethyl acetate fraction of Zingiber officinale extract (ZOE) suppressed the expression of the hTERT and c-Myc proteins, leading to the reduced telomerase activity in A549 lung cancer cells.3 In this report, we demonstrate that long-term treatment with subcytotoxic doses of ZOE, which allowed A549 cells to proliferate normally, induced telomere shortening corresponding with ZOE-induced telomerase suppression. The telomere shortening consequently induced cellular senescence in these cells, which was shown by the increase in the senescence associated β-galactosidase positive cells and the reduction in clonogenicity. In order to find the telomerase suppressors in ZOE, we employed assay-guided fractionation and GC/MS analysis to identify the chemical components. We found that the major compounds in all active subfractions contained paradols and shogaols of different chain lengths. We have concluded that the telomerase suppressors in ZOE are likely to be paradols and shogaols. Altogether, these results suggest ZOE could potentially be used as a dietary phytochemical for cancer prevention.
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