Accurate detection of butyrylcholinesterase (BChE) activity is imperative to understand its biological function and diagnose related disease. Far-red (FR)/Near-Infrared (NIR) fluorescent probe with large Stokes shift for BChE detection is extremely important. In this study, we reported a new "off-on" FR/NIR fluorescent probe (DX-2) with large Stokes shift (110 nm). DX-2 was constructed through cyclopropionate to pull-push the optical tuable hydroxyl group of chloro-substituted dicyanoisophorone fluorophore. DX-2 (λ_ex/λ_em = 555/665 nm) featured high sensitivity (LOD∼0.08 U/mL) and selectivity, good pH practicability, low toxicity and good cell membrane permeability with a bright emission triggered by BChE. Furthermore, DX-2 exhibited good optical performance to image BChE activity in living cells. More importantly, the FR/NIR probe DX-2 was successfully applied to real-time monitor BChE in live tumor-bearing mouse model. These studies suggest that probe DX-2 has potential applicable value for detecting BChE in living biological systems and diagnosing BChE-related diseases.

2011-07-01·Cancer Chemotherapy and Pharmacology4区 · 医学

Synergistic interactions between peloruside A and other microtubule-stabilizing and destabilizing agents in cultured human ovarian carcinoma cells and murine T cells

4区 · 医学

Article

作者: Clarissa Chandrahasen ; Ian Paterson ; Ariane Chan ; Anne Camille La Flamme ; Peter T. Northcote ; David O’Sullivan ; John H. Miller ; Anja Wilmes

PURPOSEMicrotubule-stabilizing agents are an important class of anticancer compounds. Peloruside A and laulimalide bind to a different site on the microtubule to taxoid site drugs such as paclitaxel (Taxol(®)), docetaxel (Taxotere(®)), ixabepilone (Ixempra(®)), the epothilones, and discodermolide. The purpose of this study was to examine the synergistic interactions of these drugs when given in combination in relation to the differences in their binding sites on the microtubule.METHODSHuman ovarian carcinoma cells (1A9 cells) and murine T cells were treated with different combinations of microtubule-stabilizing or destabilizing agents. The compounds were given individually and in combination, and the antiproliferative activity was assessed to calculate a combination index (CI) from the equation: CI = D(1)/Dx(1) + D(2)/Dx(2) in which D(1) and D(2) are the concentrations of drug 1 and drug 2 that when given together give the same response as drug 1 and 2 alone (Dx(1) and Dx(2)). Thus, a CI value of less than 1.0 indicates a synergistic effect between the two drugs in which the response to the two drugs given together is greater than the additive response of the two drugs if given on their own.RESULTSAs anticipated from previous in vitro studies, peloruside A and laulimalide did not synergize with each other. They also failed to synergize with the microtubule-destabilizing agents vinblastine and 2-methoxyestradiol. Peloruside A and laulimalide did, however, synergize with the epothilones, as had been previously shown, but not with docetaxel or discodermolide.CONCLUSIONSCombining two microtubule-targeting agents with different binding sites does not guarantee a synergistic interaction in cells, and additional factors are likely to be involved. This study highlights the importance of preclinical testing of actual combinations of drugs before proceeding into clinical trials.

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