Abstract
We tested the hypothesis that Tamoxifen (TMX), an inhibitor of protein kinase C (PKC), augments the cytotoxicity of photodynamic therapy (PDT) treatment of human (U87) and (U25ln) glioma cells. U87 and U251n glioma cells were plated and treated with PDT using Photofrin as the sensitizer. Cells were treated with Photofrin at various doses and with various optical (632 nm) irradiation intensities 24 h later. Cells were also treated with Photofrin at a fixed dose alone and with various doses of Tamoxifen and subjected to laser treatment 24 h later. Tumor response was tested using the (3-94,5-dimethyl-2-yl)-2,5-diphenyl-tetrazolium (MTT) method. Total toxicity of U87 cells was achieved with PDT at all doses of Photofrin (1, 2.5, 5, 10 μg/ml) with irradiation densities equal to or greater than 200 mJ/cm2. Using an irradiation intensity of 100 mJ/cm2, U87 and U251n cells were killed in a Photofrin dose-dependent manner. Significant cytotoxicity was detected with Photofrin doses of 5 μg/ml (p < 0.05) and 10 μg/ml (p < 0.001). Tamoxifen at a dose of 500 μg/ml and higher, significantly increased the toxicity of the PDT response with 5 μg/ml Photofrin and 100 mJ/cm2 (p < 0.05). In summary, our data demonstrate that Tamoxifen significantly enhances the Photofrin PDT activity of U87 and U251n human glioma cells.
Similar content being viewed by others
References
Black PM: Brain tumors. N Engl J Med 324: 1471-1476, 1991
Barth RF, Soloway AH, Fairchild RG: Boron neutron capture therapy of cancer. Cancer Res 50: 1061-1070, 1990
Chang SC, Bown SG: Photodynamic therapy: applications in bladder cancer and other malignancies. J Formos Med Assoc 96: 853-863, 1997
Muller PJ, Wilson BC: Photodynamic therapy for recurrent supratentorial gliomas. Seminars in Surgical Oncol 11: 346-354, 1995
Henderson BW, Dougherty TJ: How dose photodynamic therapy? Photochem Photobiol 55: 145-157, 1992
Muller PJ, Wilson BC: Photodynamic therapy for malignant newly diagnosed supratentorial gliomas. J Clin Laser Med Surg 14: 263-270, 1996
Power SK, Cush SS, Walsted DL, Kwock L: Stereotactic intratumoral photodynamic therapy for recurrent malignant brain tumors. Neurosurgery 29: 688-696, 1991
Chopp M, Dereski MO, Madigan L, Jiang F, Logie B: Sensitivity of 9L gliosarcomas to photodynamic therapy. Radiation Res 146: 461-465, 1996
Jiang F, Lilge L, Grenier J, Li Y, Wilson M, Chopp M: Photodynamic therapy of U87 human glioma in nude rat using liposome-delivered photofrin. Laser Surg Med 22: 74-80, 1998
Jiang F, Lilge L, Belcuig M, Singh G, Grenier J, Li Y, Chopp M: Photodynamic therapy using photofrin in combination with buthionine sulfoximine (BSO) to treat 9L gliosarcoma in rat brain. Laser Surg Med 23: 161-166, 1998
Azzi A, Boskoboinik D, Hensey C: The protein kinase C family. Europ J Biochem 208: 547-557, 1992
Blobe GC, Obeid LM, Hannun YA: Regulation of protein kinase C and role in cancer biology. Cancer Metastas Rev 13: 411-431, 1994
Couldwell WT, Antel JP, Apuzzo MLJ, Yong VW: Enhanced protein kinase-C activity determines the growth rate of malignant human gliomas. J Neurosurg 74: 368A, 1991
Nishizuka Y: The molecular heterogeneity of protein kinase C and its implications in cellular regulation. Nature 334: 661-665, 1988
Couldwell WT, Hinton DR, He S: Protein kinase inhibitors induce apoptosis in human malignant glioma lines. FEBS Lett 345: 43-46, 1994
Chambers TC, Pohl J, Raynor RL, Juo JF: Identification of specific sites in human P-glycoprotein phosphorylated by protein kinase C. J Biol Chem 268: 4592-4595, 1993
Zhang W, Yamada H, Sakai N, Niikawa S, Nozawa Y: Enhancement of radiosensitivity by tamoxifen in C6 glioma cells. Neurosurgery 31: 125-130, 1992
Baltuch GH, Dooley NP, Couldwell WT, Yong VW: Staurosporine differentially inhibits glioma versus nonglioma cell lines. J Neurooncol 16: 141-147, 1993
Baltuch GH, Couldwell WT, Villemure JG, Yong VW: Protein kinase C inhibitors suppress cell growth in established and low passage cell lines. A comparison between staurosporine and tamoxifen. Neurosurgery 33: 495-501, 1993
Del Prete SA, Maurer LH, O'Donnell J, Forcier RJ, LeMarbre P: Combination chemotherapy with cisplatin, carmustine, dacarbazine, and tamoxifen in metastatic melanoma. Cancer Treat Rep 68: 1403-1405, 1984
Cocconi G, Bella M, Calabresi F, Tonato M, Canaletti R, Boni C, Buzzi F, Ceci G, Corgna E, Costa P: Treatment of metastatic malignant melanoma with dacarbazine plus tamoxifen. N Engl J Med 327: 516-523, 1992
Vertosick FT, Selker RG, Pollack IF, Arena V: The treatment of intracranial malignant glioma using orally administered tamoxifen therapy: Preliminary results in a series of 'failed' patients. Neurosurgery 30: 897-903, 1992
Narasimhan P: Tamoxifen in the treatment of refractory lymphoma. N Engl J Med 311: 1258-1259, 1984
Cheng AL, Chuang SE, Fine RL, Yeh KH, Liao CM, Lay JD, Chen DS: Inhibition of the membrane translocation and activation of protein kinase C, and potentiation of doxorubicin-induced apoptosis of hepatocellular carcinoma cells by tamoxifen. Biochem Pharmacol 55: 523-531, 1998
Ponten J, Macintyre EH: Long term culture of normal and neoplastic human glia. Acta Pathol Microbiol Scand 78: 465-486, 1968
Johnston KM, Jacoby D, Pechan PA, Fraefel C, Borghesani P, Schuback D, Dunn RJ, Smith FI, Breakefield XO: HSV/AAV hybrid amplicon vectors extend transgene expression in human glioma cells. Human Gene Therapy 8: 359-370, 1997
Ahmad S, Mineta T, Martuza RL, Glazer RI: Antisense expression of protein kinase C inhibits the growth and tumorigenicity of human glioblastoma cells. Neurosurgery 35: 904-909, 1994
May WS, Tyler PG, Ito T, Armstrong DK, Qatsha KA, Davidson NE: Interleukin-3 and bryostatin-1 mediate hyperphosphorylation of BCL2a in association with suppression of apoptosis. J Biol Chem 269: 26865-26870, 1994
Leris C, Mokbel K: The prevention of breast cancer: an overview. Curr Med Res Opin 16(4): 252-257: 2001
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Jiang, F., Cho, KK., Mikkelsen, T. et al. Tamoxifen Increases Photodynamic Therapeutic Response of U87 and U25ln Human Glioma Cells. J Neurooncol 56, 51–58 (2002). https://doi.org/10.1023/A:1014400822235
Issue Date:
DOI: https://doi.org/10.1023/A:1014400822235