A Cisplatin Derivative Tetra-Pt(bpy) as an Oncotherapeutic Agent for Targeting ALT Cancer

Journal of the National Cancer Institute
Xiao-Hui ZhengYong Zhao

Abstract

In approximately 15% of human cancers, telomere length is maintained independently of telomerase by the homologous recombination (HR)-mediated alternative lengthening of telomeres (ALT) pathway. Whether the ALT pathway can be exploited for therapeutic treatment remains unknown. The purpose of this study is to develop oncotherapeutic agent to target ALT cancers. Surface plasmon resonance assay, antibody to G-quadruplex, and fluorescence in situ hybridization (FISH) were used to discover Tetra-Pt(bpy), a cisplatin derivative that specifically targets telomeric G-quadruplex. We used immunofluorescence, FISH, C-circle assay, and chromosome orientation FISH to evaluate the inhibitory effect of Tetra-Pt(bpy) on ALT activity in human ALT cancers. The shortening of telomere length induced by Tetra-Pt(bpy) was determined by telomere restriction fragment or Q-FISH. Cell destination after Tetra-Pt(bpy) treatment was determined by β-gal staining or apoptosis assay. Nude mice (n = 4 per group) were injected with U2OS cells to evaluate the effects of Tetra-Pt(bpy) on tumor growth. All statistical tests were two-sided. Tetra-Pt(bpy) inhibits the strand invasion/annealing step of telomeric homologous recombination by selectively converting tel...Continue Reading

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Citations

Apr 13, 2019·Nucleic Acids Research·Miaomiao ZhangFeng Wang
Feb 6, 2020·Genes·Aurore Sommer, Nicola J Royle
Apr 13, 2018·Nucleic Acids Research·Marko TrajkovskiNaoki Sugimoto
May 8, 2020·Journal of Experimental & Clinical Cancer Research : CR·S L GeorgeL Chesler
Apr 16, 2020·Cancer Research·Balakrishna KoneruC Patrick Reynolds
Jun 3, 2021·International Journal of Molecular Sciences·Irene AlessandriniMarco Folini
Aug 28, 2021·Biomolecules·Jesmin Akter, Takehiko Kamijo
Aug 31, 2021·International Journal of Biological Macromolecules·Min ZouChun-Qiong Zhou
Oct 13, 2021·International Journal of Cancer. Journal International Du Cancer·Sabine A Stainczyk, Frank Westermann
Dec 17, 2021·Journal of Cellular and Molecular Medicine·Jing-Yi ChenXiao-Hui Zheng

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