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Radiosensitization by nickel lapachol

K A Skov¹, H Adomat, N P Farrell

¹B. C. Cancer Research Centre, Vancouver, Canada.

International Journal of Radiation Biology

|December 1, 1993

Summary

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Nickel lapachol and misonidazole exhibit similar radiosensitization properties, including reduction potential and cell killing enhancement in hypoxic conditions. This suggests novel therapeutic applications for metal complexes in cancer treatment.

Area of Science:

Biochemistry
Radiotherapy
Medicinal Chemistry

Background:

Radiosensitizers enhance the efficacy of radiation therapy.
Nitroimidazoles are established radiosensitizers, functioning via electron affinity.
Metal complexes offer alternative mechanisms for radiosensitization.

Purpose of the Study:

To compare the radiosensitizing properties of nickel lapachol with the established nitroimidazole, misonidazole.
To investigate the mechanisms underlying the radiosensitization effects of nickel lapachol.

Main Methods:

Comparative analysis of reduction potentials.
Assessment of cell killing enhancement in hypoxic Chinese hamster ovary cells using X-irradiation.
Evaluation of DNA break enhancement in hypoxic conditions.

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Main Results:

Nickel lapachol and misonidazole demonstrated similar reduction potentials (-370 mV).
Both compounds showed comparable enhancement ratios for killing hypoxic cells and DNA breaks.
Nickel lapachol exhibited additional radiosensitizing activities in aerobic cells and with preincubation.

Conclusions:

Nickel lapachol functions as an effective radiosensitizer, comparable to misonidazole, through a distinct mechanism involving the metal component.
The naphthoquinone ligand may contribute to nickel lapachol's unique radiosensitizing activities.
Nickel lapachol presents a promising alternative or adjunct to traditional nitroimidazole radiosensitizers.