ISSN:
1437-7772
Keywords:
Key words Photodynamic therapy
;
Cervical cancer
;
Apoptosis
;
MnSOD
;
Gene induction
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Background. Photodynamic therapy (PDT) is a cancer treatment modality in which systemic administration of a tumor-localizing photosensitizer is followed by irradiation of the tumor with visible light. Although PDT is undergoing clinical trials for various cancers, the mechanisms of its action are not fully understood. To investigate the mechanism of cell death by PDT, we performed in-vitro PDT, using Photofrin II as a photosensitizer, in two human cervical carcinoma cell lines, HeLa and CaSki. Methods. Cells were incubated with Photofrin II for 24 h, followed by illumination, using a YAG-OPO laser. Cell survivability after PDT was evaluated by an MTT assay. Cytotoxicity was assayed by measuring the release of lactate dehydrogenase (LDH) into the supernatant. DNA of the PDT-treated cells was electrophoresed in an agarose gel to determine fragmentation. In situ detection of apoptosis in the PDT-treated cells was performed by identification of the 3′-OH ends of DNA. In addition, induction of manganese superoxide dismutase mRNA (MnSOD) was analyzed in the PDT-treated cells. Results. The CaSki cells were more sensitive to this PDT treatment than were the HeLa cells. DNA fragmentation was observed with less than 5 μg/ml of Photofrin II in both cell lines, whereas PDT-induced cell membrane destruction, determined by LDH release, was observed only at 10 μg/ml. The MnSOD mRNA was induced in the HeLa cells in the early hours after PDT with a non-lethal dose of Photofrin II, but was reduced with a high dose, whereas the CaSki cells did not show any induction of the MnSOD gene by PDT. Conclusion. The present results suggest that PDT induces cell death by a mechanism involving membrane destruction and apoptosis. Differences in cell susceptibilities to PDT may depend upon a protective mechanism, such as MnSOD gene induction.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s101470050098
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