Sulforaphane decreases viability and telomerase activity in hepatocellular carcinoma Hep3B cells through the reactive oxygen species-dependent pathway.
Sulforaphane (SFN), a dietary isothiocyanate, is a well known natural product that possesses anti-cancer and chemopreventive activities. However, the molecular mechanism of the anti-telomerase activity of SFN is not well understood. In this study, we investigated the hypothesis that SFN inhibits cell viability and telomerase activity via downregulation of telomerase reverse transcriptase (hTERT) expression. We suggest that elevated intracellular reactive oxygen species (ROS) levels, due to exposure to SFN, has a critical role in abolishing since pretreatment with NAC, an antioxidant, resulted in the recovery of hTERT expression. SFN also suppressed the phosphorylation of Akt (Ser-473), thereby inhibiting hTERT phosphorylation and this effect was reversed by pretreatment with NAC. Taken together, these data suggest that ROS are essential for the suppression of SFN-mediated telomerase activity via transcriptional and posttranslational regulation of hTERT.
Moon
Dong-Oh
DO
Department of Marine Life Sciences, Jeju National University, Republic of Korea.
Kang
Sang-Hyuck
SH
Kim
Ki-Cheon
KC
Kim
Mun-Ock
MO
Choi
Yung Hyun
YH
Kim
Gi-Young
GY
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D006801:Humans; D017879:Isothiocyanates; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013454:Sulfoxides; D019098:Telomerase / Q000037:antagonists & inhibitors*; D013861:Thiocyanates / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D017382:Reactive Oxygen Species; D013454:Sulfoxides; D013861:Thiocyanates; D051057:Proto-Oncogene Proteins c-akt; C509186:TERT protein, human; D019098:Telomerase; C016766:sulforaphane