Selected ellipticine derivatives, known to target topoisomerase II, suppress the alternative lengthening of telomere (ALT) pathway in telomerase

Article Article scientifique Article Selected ellipticine derivatives, known to target topoisomerase II, suppress the alternative lengthening of telomere (ALT) pathway in telomerase–negative cells eng 2020-04-24 2020-07 author Zencir Sevil Department of Molecular Biology, University of Geneva, CH-1211, Geneva 4, Switzerland. sevil.zencir@unige.ch.,Department of Medical Biology, Faculty of Medicine, Pamukkale University, 20020, Denizli, Turkey. sevil.zencir@unige.ch. 909667 author Hsieh Meng-Hsun Department of Microbiology, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan. author Hsu Joel-Sean 0000-0002-7621-4713 Department of Microbiology, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan. author Ergun Yavuz Department of Chemistry, Faculty of Science, Dokuz Eylul University, 35160, Izmir, Turkey. author Chou Guan-Ling Department of Microbiology, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan. author Li Tsai-Kun Department of Microbiology, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan. author Teng Shu-Chun Department of Microbiology, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan. author Topcu Zeki Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Ege University, 35100, Izmir, Turkey. 1671-1676 10.1007/s00432-020-03213-x 32333143 0171-5216 PMC11804416 https://link.springer.com/10.1007/s00432-020-03213-x Background: DNA topoisomerase and telomerase enzymes are popular targets of several anti-tumor drugs. Smooth proceeding of telomeric recombination requires Topoisomerase II (Top2), which is involved in telomere-telomere recombination through functioning in relaxation of positive supercoils among the cells adopting telomerase-independent Alternative lengthening of telomere (ALT) pathway. Most of the inhibitors reported so far have been designed to targetsolely telomerase-positive cells, which can potentially lead to therapeutic failure because tumor cells treated with telomerase inhibitors can activate the ALT pathway for telomere maintenance. Knowing that ALT cells are more sensitive against a Top2 inhibitor, ICRF-93 agent, compared to telomerase-positive cells, we analyzed two selected ellipticine derivatives that we recently reported as TopII-targeting compounds, to assess their effects on the formation of DNA breaks and suppression of ALT pathway. Methods: Cell viability, Comet, C-Circle assays, dot blot, immunofluorescence staining, and telomere fluorescence in situ hybridization (FISH) staining were used for determining the effect of the compounds on ALT status of tumor cells. Results and conclusions: Treatment of ALT cells with ellipticine derivatives resulted in the formation of DNA breaks and suppression of ALT-associated phenotypes in vitro. Our results will contribute to the development of therapeutic strategies combining telomerase and ALT pathway inhibitors. Alternative lengthening of telomere Anti-cancer therapeutics DNA topoisomerase II Ellipticine derivatives Dewey 610 Dewey 570 7daed2ee-1311-4824-9df9-2e51260a966a Département de biologie moléculaire et cellulaire 16484 3 Faculté de médecine 2 false Journal of cancer research and clinical oncology 146 7 2df460e7-a1bc-4c66-af74-af4337bb8ce1 Article (Published version) Restricted Article_scientifique_from_crossref.pdf 1052090 application/pdf 192d55cd701b172279b4f66f9598df34195bf6c2204fa0a0ddfd025fcc8efb1b restrictedAccess Faculté des sciences / Section de biologie / Département de biologie moléculaire et cellulaire Faculté de médecine

Title	Published in	Access level	OA Policy	Year	Views	Downloads

Selected ellipticine derivatives, known to target topoisomerase II, suppress the alternative lengthening of telomere (ALT) pathway in telomerase–negative cells	Journal of cancer research and clinical oncology			2020	4	0

Archive ouverte UNIGE

Zencir, Sevil