Ginger Extract Promotes Telomere Shortening and Cellular Senescence in A549 Lung Cancer Cells

Navakoon Kaewtunjai; Rawiwan Wongpoomchai; Arisa Imsumran; Wilart Pompimon; Anan Athipornchai; Apichart Suksamrarn; T Randall Lee; Wirote Tuntiwechapikul

doi:10.1021/acsomega.8b02853

Ginger Extract Promotes Telomere Shortening and Cellular Senescence in A549 Lung Cancer Cells

ACS Omega. 2018 Dec 27;3(12):18572-18581. doi: 10.1021/acsomega.8b02853. eCollection 2018 Dec 31.

Authors

Navakoon Kaewtunjai¹, Rawiwan Wongpoomchai¹, Arisa Imsumran¹, Wilart Pompimon², Anan Athipornchai³, Apichart Suksamrarn⁴, T Randall Lee⁵, Wirote Tuntiwechapikul¹

Affiliations

¹ Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
² Laboratory of Natural Products, Department of Chemistry, Faculty of Science and Center of Innovation in Chemistry, Lampang Rajabhat University, Lampang 52100, Thailand.
³ Department of Chemistry, Center of Excellence for Innovation in Chemistry, Burapha University, Chon Buri 20131, Thailand.
⁴ Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok 10240, Thailand.
⁵ Department of Chemistry and the Texas Center for Superconductivity, University of Houston, Houston, Texas 77204-5003, United States.

Abstract

Replicative senescence, which is caused by telomere shortening from the end replication problem, is considered one of the tumor-suppressor mechanisms in eukaryotes. However, most cancers escape this replicative senescence by reactivating telomerase, an enzyme that extends the 3'-ends of the telomeres. Previously, we reported the telomerase inhibitory effect of a crude Zingiber officinale extract (ZOE), which suppressed hTERT expression, leading to a reduction in hTERT protein and telomerase activity in A549 lung cancer cells. In the present study, we found that ZOE-induced telomere shortening and cellular senescence during the period of 60 days when these A549 cells were treated with subcytotoxic doses of ZOE. Using assay-guided fractionation and gas chromatography/mass spectrometry analysis, we found that the major compounds in the active subfractions were paradols and shogaols of various chain lengths. The results from studies of pure 6-paradol and 6-shogaol confirmed that these two compounds could suppress hTERT expression as well as telomerase activity in A549 cells. These results suggest that these paradols and shogaols are likely the active compounds in ZOE that suppress hTERT expression and telomerase activity in these cells. Furthermore, ZOE was found to be nontoxic and had an anticlastogenic effect against diethylnitrosamine-induced liver micronucleus formation in rats. These findings suggest that ginger extract can potentially be useful in dietary cancer prevention.