Neoplasma Vol.52, p.352-359, 2005
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Title: Diazepam enhances hypericin-induced photocytotoxicity and apoptosis
in human glioblastoma cells
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Author: M., SARISSKY
; J., LAVICKA
; S., KOCANOVA
; I., SULLA
; A., MIROSSAY
; P., MISKOVSKY
; M., GAJDOS
; J., MOJZIS
; L., MIROSSAY
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Abstract: Glioblastoma multiforme (GBM) is neoplasm which is resistant to
all currently used treatment modalities including surgery,
radiation therapy and chemotherapy. Photodynamic therapy (PDT) has
been suggested as a novel therapeutical approach
to the treatment of malignant gliomas. Here, we attempted to
enhance hypericin-induced photocytotoxicity and
apoptosis by diazepam, a non-selective ligand of peripheral
benzodiazepine receptors (PBR) which seem to play an important
role in apoptosis regulation.
For the study, we used U-87 MG and U373 MG glioma cell lines and
primary cultures of GBM cells prepared from
peroperatively obtained tumor specimens. The patients included 7
histologically confirmed GBMs. Colorimetric MTT assay
was employed to study the photocytotoxic effects of hypericin and
diazepam. Flow cytometry was used to detect
apoptosis and assess the proapoptotic effects of diazepam.
We found that hypericin upon photoactivation exerts strong
cytotoxic effects against U-87 MG and U373 MG cells as
well as primary GBM cell cultures. No cytotoxic effect of
hypericin was observed under dark conditions. Diazepam inhibited
cell growth in U-87MGcells and primary cultures whereas
proliferation of U373MGcells remained unaffected. When
hypericin was combined with diazepam, photocytotoxicity was
increased in U-87 MG cells and primary cultures unlike
U373MGcells. Flow cytometric analysis revealed photoactivated
hypericin-induced apoptosis in both cell lines. Apoptosis
was significantly enhanced by diazepam in U-87 MG cells. However,
no such effect was observed in U373 MG cells.
In the present study, we showed that photocytotoxic effect of
hypericin in glioma cells can be potentiated by diazepam.
This effect is underlied by the ability of diazepam to facilitate
hypericin-induced apoptosis. This work provides support to
performe clinical studies involving diazepam in the antiglioma
treatment regimens as an apoptosis-modulating agent.
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Keywords: apoptosis, glioma, hypericin, diazepam, peripheral benzodiazepine
receptor, photodynamic therapy
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Year: 2005, Volume: 52, Issue: |
Page From: 352, Page To: 359 |
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