title: Fluorescence spectral properties of the anticancer drug topotecan by steady-state and frequency domain fluorometry with one-photon and multi-photon excitation.
abstract: Topotecan is an antitumor agent with activity against a variety of cancers. We examined the steady-state and time-resolved fluorescence spectral properties of topotecan with one- and two-photon excitation. Topotecan was found to display a high two-photon cross section near 20 GM for wavelengths within the fundamental output of a Ti:sapphire laser, 800-880 nm. In frozen solution the anisotropies of topotecan are near the theoretical maxima for one-photon and two-photon excitation with colinear electronic transitions. The intensity and anisotropy decays of topotecan fluorescence were found to be homogeneous (single exponentials) in phosphate-buffered saline and propylene glycol. The steady-state and time-resolved data indicate that topotecan binds to a double-helical DNA oligomer d(AT)10 resulting in increased anisotropies and multiexponential intensity and anisotropy decays. Subnanosecond components in the anisotropy decay of the DNA-topotecan complex suggest loose binding of the drug to DNA. Loose binding of topotecan to DNA is also revealed by accessibility of topotecan to collisional quenching by iodide.
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Maryland School of Medicine, Baltimore 21201, USA.
authors.forename: I
authors.initials: I
authors.lastname: Gryczynski
authors.forename: Z
authors.initials: Z
authors.lastname: Gryczynski
authors.forename: J R
authors.initials: JR
authors.lastname: Lakowicz
authors.forename: D
authors.initials: D
authors.lastname: Yang
authors.forename: T G
authors.initials: TG
authors.lastname: Burke
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000528:radiation effects*; D004247:DNA / Q000378:metabolism; D005454:Fluorescence Polarization; D006801:Humans; D066298:In Vitro Techniques; D010777:Photochemistry; D017785:Photons; D013050:Spectrometry, Fluorescence; D019772:Topotecan / Q000737:chemistry* / Q000378:metabolism / Q000528:radiation effects*
chemical_list: D000970:Antineoplastic Agents; D019772:Topotecan; D004247:DNA