Multiple modality treatment of carcinoma cells with Pt(Rh-123)2 plus x-ray plus light.
A complex of platinum tetrachloride with two molecules of rhodamine-123 (Rh-123), Pt(Rh-123)2, has been reported to act as hypoxic cell radiosensitizer of carcinoma cells in vitro and in vivo. In the present paper we report that Pt(Rh-123)2 photosensitizes human mammary carcinoma (MCF-7) cells and cis-platinum resistant human mammary carcinoma (MCF-7/CP) cells to 400-800 nm light in vitro. The efficiency of photosensitization by Pt(Rh-123)2 was 10 times greater than for Rh-123. Combination therapy using Pt(Rh-123)2 plus x-ray plus light was also much more effective compared to the combination therapy using Rh-123 plus x-ray plus light. After 15 microM of Rh-123 plus x-ray (0-8 Gy) plus light (5 J/cm2) treatment, cell survival curve was parallel to the x-ray cell survival curve with an initial decrease in the surviving fraction corresponding to the drug plus light mediated killing. Cell killing caused by Rh-123 (15 microM) plus x-ray (0-8 Gy) plus light (5 J/cm2) was additive as determined by the product of the surviving fraction after Rh-123 plus light and x-ray. In contrast, for 15 microM of Pt(Rh-123)2 plus x-ray (8 Gy) plus light (5 J/cm2) treatment, whereas additive killing predicts a survival fraction of approximately 0.024, in reality, the combination therapy caused the survival fraction to decrease to 0.0012, implying that the cell killing was enhanced by a factor of 20. Using Pt(Rh-123)2 plus x-ray plus light, supra-additive cell killing was also observed under hypoxic conditions, although compared to normally oxygenated conditions the degree of cytotoxicity was significantly reduced.(ABSTRACT TRUNCATED AT 250 WORDS)
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Division of Cancer Pharmacology, Dana Farber Cancer Institute, Boston, MA 02115.
Varshney
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Ha
C S
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Oseroff
A R
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Herman
T S
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Teicher
B A
BA
D000230:Adenocarcinoma; D001692:Biological Transport; D001943:Breast Neoplasms; D015687:Cell Hypoxia; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects; D002945:Cisplatin / Q000494:pharmacology*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007700:Kinetics; D008027:Light; D008954:Models, Biological; D009944:Organoplatinum Compounds / Q000378:metabolism / Q000494:pharmacology*; D010778:Photochemotherapy; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D020112:Rhodamine 123; D012235:Rhodamines / Q000378:metabolism / Q000494:pharmacology*; D014965:X-Rays
D009944:Organoplatinum Compounds; D011838:Radiation-Sensitizing Agents; D012235:Rhodamines; C050316:tetrachloroplatinate dianion-rhodamine-123 complex; D020112:Rhodamine 123; D002945:Cisplatin