Antitumour effect of MX2, a new morpholino anthracycline against C6 glioma cells and its cytotoxic effect in combination with photodynamic therapy.
MX2, a novel lipophilic morpholino anthracycline, has been reported to have superior chemotherapeutic effects to Adriamycin (ADM) against murine and human tumour cells. In this study the chemotherapeutic effect of MX2 against C6 glioma cells in vitro and in vivo was examined as well as the photocytotoxicity of MX2 and the combination effect of MX2 and photodynamic therapy (PDT) in vitro. The drug concentration required for 50% inhibition of cell growth (IC50) of MX2 for C6 glioma cells was 6.5 +/- 1.0 ng/ml, which was lower than for ADM and nitrosourea (ACNU). The growth of C6 glioma cells inoculated intracerebrally in mice was inhibited by intravenous (iv) injection of MX2 at doses ranging from 1.0-3.0 mg/kg suggesting that MX2 may be clinically effective against human malignant gliomas. Mild photocytotoxicity of MX2 against C6 cells in vitro was observed at high concentrations of MX2 illuminated with white light but not red light (> 630 nm). In combination, MX2 and the photosensitizer haematoporphyrin derivative (HpD) resulted in cyto- and photo-toxicity of C6 glioma cells irrespective of whether the cells were treated with MX2 either immediately after red light illumination following incubation with HpD, or at an interval of 24 hours before incubation with HpD. We conclude that MX2 may be clinically useful against malignant glioma alone, and in combination with other therapies such as PDT.
Kabuto
M
M
Department of Neurosurgery, Higginbotham Neuroscience Research Institute and Department of Surgery, Clinical Neuroscience Centre, Royal melbourne Hospital, Melbourne, Australia.
Kaye
A H
AH
Hill
J S
JS
Stylli
S S
SS