Activity of phthalocyanine photosensitizers against human glioblastoma in vitro.
In vitro studies utilizing an established human glioblastoma cell line (U87MG) were undertaken to compare the light absorption spectra and photocytotoxicity characteristics of hematoporphyrin derivative (HpD), metal-free phthalocyanine tetrasulfonate (PcS), and aluminum phthalocyanine tetrasulfonate (AlPcS). The peak absorption wavelengths for the compounds studied were: HpD = 630 nm, PcS = 630 nm, AlPcS = 677 nm. Seven different concentrations of each compound (0 to 20 micrograms/ml) were subjected to five different energy levels (40 to 640 joules/cm2) of broad band light (wavelength = 650 +/- 40 nm). Control experiments employing each drug alone and photoactivation alone were also performed. HpD showed a consistent dose-dependent photoactivated cytotoxicity with an abrupt decrease in cell survival when energies of 160 joules/cm2 or more were administered and a drug concentration dependency that resulted in a progressive decline in cell survival beginning at 1.0 microgram/ml. The metal-free PcS had a 10 times greater absorption of light at 675 nm, but only a very weak cytotoxic effect, which occurred at concentrations in excess of 10.0 micrograms/ml and energy levels greater than 320 joules/cm2. AlPcS, however, displayed a 100-fold increase in light absorption at 675 nm when compared to HpD. This was coupled with a decrease in cell survival similar to the HpD curves, but with a much steeper slope of percentage cell kill at lower drug concentrations and energy dosages. The control studies did not result in any appreciable cytotoxic effect. The data suggest that AlPcS holds promise as a second generation photosensitizer in the photodynamic treatment of human gliomas.
Abernathey
C D
CD
Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota.
Anderson
R E
RE
Kooistra
K L
KL
Laws
E R
ER
D001932:Brain Neoplasms / Q000188:drug therapy; D002470:Cell Survival; D005910:Glioma / Q000188:drug therapy*; D006414:Hematoporphyrin Photoradiation; D006801:Humans; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D009942:Organometallic Compounds / Q000494:pharmacology / Q000627:therapeutic use; D010778:Photochemotherapy; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D007211:Indoles; D009942:Organometallic Compounds; C048577:aluminum tetrasulfophthalocyanine; C028418:tetrasulfophthalocyanine