Toxicity and cytopathogenic properties toward human melanoma cells of activated cancer therapeutics in zebra fish

Integr Cancer Ther. 2010 Mar;9(1):84-92. doi: 10.1177/1534735409355171.

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.

MeSH terms

  • Animals
  • Apoptosis* / drug effects
  • Combined Modality Therapy / adverse effects
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Humans
  • Melanoma / pathology*
  • Melanoma / therapy*
  • Photochemotherapy* / adverse effects
  • Radiation-Sensitizing Agents / adverse effects
  • Radiation-Sensitizing Agents / therapeutic use
  • Treatment Outcome
  • Tumor Cells, Cultured
  • Ultrasonic Therapy* / adverse effects
  • Xenograft Model Antitumor Assays
  • Zebrafish*

Substances

  • Radiation-Sensitizing Agents