Camptothecin induces c-Myc- and Sp1-mediated hTERT expression in LNCaP cells: Involvement of reactive oxygen species and PI3K/Akt.

Camptothecin induces c-Myc- and Sp1-mediated hTERT expression in LNCaP cells: Involvement of reactive oxygen species and PI3K/Akt. Food Chem Toxicol. 2019 Mar 06;: Authors: Dilshara MG, Jayasooriya RGPT, Choi YH, Kim GY Abstract Camptothecin (CPT), a quinoline alkaloid isolated from Camptotheca acuminate, targets topoisomerase I, which is continuously expressed in cancer cells. However, the molecular mechanisms responsible for CPT-induced telomerase inhibition remain unclear. Unexpectedly, we found that CPT upregulates hTERT expression and concomitantly increases telomerase activity. However, transfection of hTERT-targeting siRNA had no effect on CPT-induced G2/M phase arrest, suggesting that CPT-induced telomerase activation was not related to G2/M phase arrest. CPT simultaneously increased Nrf2 expression and the level of intracellular reactive oxygen species (ROS), whereas pretreatment with the antioxidants N-acetyl-cysteine (NAC) or glutathione (GSH) strongly attenuated ROS production, which was accompanied by hTERT downregulation. Additionally, transient Nrf2 knockdown enhanced CPT-induced ROS production and hTERT promoter activity. CPT also upregulated hTERT expression and telomerase activity by inducing c-Myc and Sp1 expression and activity. Moreover, c-Myc stimulated ROS production in response to CPT, leading to Sp1 activation, which promoted hTERT expression and telomerase activity. CPT treatment enhanced the phosphorylation...
Source: Food and Chemical Toxicology - Category: Food Science Authors: Tags: Food Chem Toxicol Source Type: research