Photodynamic enhancement of doxorubicin cytotoxicity

Abstract

Argon ion laser irradiation at 514.1 nm and 488 nm dramatically increased doxorubicin cytotoxicity in an L929 cell clonogenic survival assay. The cytotoxicity was dependent on both the drug concentration and the total light energy delivered such that at 5 micrograms doxorubicin/ml and 800 J/cm2, cytotoxicity was enhanced by a factor of > 10(4) relative to that achieved with drug alone. Irradiation times in excess of 2 min and power densities in excess of 100 J/cm2 were required to produce the effect. Beyond this 2-min limit, cytotoxicity was not related to the duration of exposure if the total energy delivered was held constant. The ability of catalase and superoxide dismutase to abolish completely the increase in cytotoxicity produced by laser irradiation suggests that the cytotoxic mechanism may depend on the generation of active oxygen species by the photodynamically excited drug.

Combined effect of low-power laser irradiation and anthraquinone anticancer drug aclarubicin on survival of immortalized cells: Comparison with mitoxantrone

“…Although we observed minor photocytotoxic effect of aclarubicin with conjunction with LPL compared to the phototoxic effects reported previously for other anthracyclines (Brophy and Keller, 1992;Canti et al, 1998;Lanks et al, 1994;Paiva et al, 1996Paiva et al, , 1998 it seems that aclarubicin might be considered as a good candidate for combined PDT, especially as in contrast to other anthracyclines (doxorubicin, daunorubicin) it displays considerably lower cardiotoxicity (Natale et al, 1993). Aclarubicin strongly absorbs light in the long wavelength region of the visible spectra, which also theoretically makes this drug a good candidate as a photosensitizer.…”

“…Poor response to PDT was observed for doxorubicin concentrations and laser power density less than the relevant threshold values (Gao et al, 1997;Lanks et al, 1994). These results suggest that to achieve significant enhancement of drug cytotoxicity it is necessary to exceed the threshold power density and the duration time of irradiation attributed to the particular cell line.…”

Transient inhibition of L929 cell mitosis and locomotion by argon ion laser irradiation

“…Recovery, as evidenced by the appearance of substantial numbers of anaphase mitoses, could be detected as early as 4 h after the lowest intensity light exposure, but recovery after the highest intensity light exposure did not occur within the 24-h time frame of this experiment. Nevertheless, clonogenic survival (6) determined after 7-10 d of culture was unaffected, i.e., 100 + 20%, at all light doses used in these experiments (5).…”

“…L929 cells were maintained in polystyrene tissue culture dishes as previously described (5). Irradiation was performed in medium ~To whom co~espondence should be addressed.…”

“…In the course of investigations into the mechanism by which argon ion laser irradiation increases doxorubicin cytotoxicity, we performed many control experiments which uniformly showed no cytocidal effects of irradiation alone when we used an in vitro L929 cell clonogenic survival assay system (5). We have subsequently noticed that even though laser irradiation has no detectable cytocidal effects on L929 cells or any other cell system that we have examined, laser irradiation alone does lead to transient inhibition of mitosis that has specific characteristics.…”