Journal Article

A Macrocyclic Zinc(II) Fluorophore as a Detector of Apoptosis

Koike, Tohru, Kikuta, Emiko, Kimura, Eiichi, Aoki, Shin

2003

Overview

Our originally designed dansylamidoethylcyclen 4 as a biomimetic Zn2+-selective fluorophore has been demonstrated to be a good detector of the apoptosis (induced by an anticancer agent, etoposide, and H2O2) in cancer cells such as HeLa and HL60 cells. The macrocyclic Zn2+ ligand 4 (mostly as a deprotonated form) is cell-permeable to show weak fluorescence (emission at 550 nm), which forms a strong fluorescent 1:1 Zn2+ complex 5 (emission at 530 nm) when Zn2+ is incorporated into the cells by a zinc(II) ionophore pyrithione. Thus formed, Zn2+ complex 5 is cell-impermeable and remains intact over a few hours. When apoptosis in HeLa or HL60 cells is artificially induced, 4 selectively and strongly stains apoptotic cells only at early stages, which was verified by using the conventional apoptosis detection probe annexin V-Cy3. Detection of the apoptotic cells by 4 was perhaps due to significantly increased free Zn2+ flux at early stages of apoptosis. Apoptotic detection by 4 has been compared with a presently available Zn2+ fluorophore, Zinquin 1. We present that 4 has advantages in detection of apoptosis over annexin V-Cy3 and Zinquin 1.

• Publisher: National Academy of Sciences,National Acad Sciences,The National Academy of Sciences
• Subject: Annexins / Apoptosis / Biochemistry / Bioinorganic Chemistry Special Feature / Biomarkers - analysis / Biomimetics / Cell membranes / Cultured cells / Dansyl Compounds - chemistry / Emissions / Fluorescence / Fluorescent Dyes / HeLa Cells / Heterocyclic Compounds, 1-Ring - analysis / Heterocyclic Compounds, 1-Ring - chemistry / HL-60 Cells / Humans / Hydrogen peroxide / Japanese culture / Ligands / Molecular Conformation / Molecular Structure / Necrosis / Organometallic Compounds - analysis / Organometallic Compounds - chemistry / Physical Sciences / Secretory cells / Zinc Compounds - analysis / Zinc Compounds - chemistry