Toxicity and Cytopathogenic Properties Toward Human Melanoma Cells of Activated Cancer Therapeutics in Zebra Fish

Abstract

There is an increasing body of data showing that activated cancer therapy-the synergistic effect of "preloaded" molecules and a tuned energy source to produce cytopathogenic moieties-is a promising new modality for cancer treatment. The key activated therapies are photodynamic therapy (PDT), which involves the synergy between light and photosensitizer molecules, and ultrasound activated therapy (USAT; also referred to as sonodynamic therapy), which involves the synergy between ultrasound and sonosensitizer molecules. PDT is a well-known activated therapy with roots dating back to 1900. However, minimal data exist on USAT. One reason is the lack of suitable sonosensitizers for clinical USAT use. The authors present both LC 50 toxicity and cancer cell cytotoxicity studies on 2 dual activation agents. These compounds function as both sonosensitizers and photosensitizers, and are referred to as SonneLux agents, designated SF1 and SF2. The sensitizers are derived from chlorophyll and are metal centered porphyrins known to specifically accumulate in hyperproliferating tissue. LC 50 studies on both SF1 and SF2 as determined in zebra fish reveal that both are essentially nontoxic to zebra fish. In the worst case, 5% zebra fish death is noted at the maximum soluble concentration of the sensitizer. In the cytotoxicity studies, melanoma cell line WM-266-4, derived from a metastatic site of a malignant melanoma, was tested against SF1 and SF2. Both sensitizer systems showed marked efficacy in the destruction of the implanted melanoma cells. They show great promise for clinical use in the future.

Macondo crude oil from the Deepwater Horizon oil spill disrupts specific developmental processes during zebrafish embryogenesis

“…The small adult fish size, large embryo clutches, ex utero development, and transparent embryo and larval stages of zebrafish enable cost effective maintenance of many fish, reproducible sample sizes, simple application of toxin treatments, and easy evaluation of end-point toxicity [14-18]. The use of zebrafish to assay drug and pollutant toxicity has already provided insights into the developmental and molecular mechanistic roles of metals [19,20], dioxins [21-24], pesticides [25,26], endocrine disruptors [27,28], alcohols [29-31], chemotherapies [32-34] and specific pharmaceutical compounds many of which were assessed via high-throughput screening [35]. …”

One step forward: The use of transgenic zebrafish tumor model in drug screens

“…Traditionally, the early stages of the drug-discovery process rely on in vitro assays, conventional highthroughput liquid chromatography (LC)-tandem mass spectrometry (MS/MS) (Weigelt, 2009; , 2010;Shou and Zhang, 2010). Although in vitro assays are effective, more and more researchers are adopting cellbased assays to address this early phase of drug development.…”

“…Another example is the identification of dorsomorphin, one of the first small-molecule compounds identified to inhibit BMP signaling, as well as its effect in increasing serum iron levels in mice and thus may prove to be a poten-tial drug in anemia treatment (Yu et al, 2008). Recently, the zebrafish was also used to test the toxicity of two SonnelLux agents and proved them to be non-toxic; these compounds function as both sonosensitizers and photosensitizers, and showed significant efficacy in destroying implanted melanoma cells (Lewis, 2010).…”

Rationale of Combined PDT and SDT Modalities for Treating Cancer Patients in Terminal Stage: The Proper Use of Photosensitizer

“…SF1 is an analog of chlorophyll in that its macrocycle backbone is porphyrin-based and the center of the porphyrin ring consists of a metal ion. 2 The chlorophyll derivative has light absorption peaks at 402 and 636 nm.…”

“…SF1 is an analog of chlorophyll in that its macrocycle backbone is porphyrin-based and the center of the porphyrin ring consists of a metal ion. 2 The chlorophyll derivative has light absorption peaks at 402 and 636 nm.3 A very unusual combination of this investigational agent and various prototype light sources and ultrasound devices was used in the treatment of three patients who suffered from late stages of breast cancer with systemic metastases to multiple organs. The combination of photosensitizer and light illumination is commonly known as photodynamic therapy (PDT) and the combination of drug or sonosensitizer and acoustic activation as sonodynamic therapy (SDT).…”