Apoptosis of human glioma cells in response to calphostin C, a specific protein kinase C inhibitor

View More View Less
  • 1 Departments of Neurosurgery and Genetics, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
Restricted access

Purchase Now

USD  $45.00

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00
Print or Print + Online

✓ Calphostin C acts at the regulatory domain as a highly selective inhibitor of protein kinase C (PKC), and staurosporine acts at the catalytic domain as a nonspecific PKC inhibitor. The authors investigated the capacity of calphostin C and staurosporine to promote apoptotic fragmentation of DNA in four human glioma cell lines. The exposure of glioma cell lines to 100 nM calphostin C for 2 to 8 hours induced a decrease in particulate PKC activities and exposure for 16 to 24 hours produced a concentration-dependent increase in internucleosomal DNA cleavage on agarose gel electrophoresis. In addition, the human glioma cells showed the classic morphological features of apoptosis: cell shrinkage, nuclear condensation, and the formation of apoptotic bodies. A 24-hour exposure to staurosporine failed to induce internucleosomal DNA fragmentation at concentrations generally used to achieve maximum inhibition of enzyme activity (50 nM) but promoted fragmentation at considerably higher concentration (more than 200 nM). Deoxyribonucleic acid fragments obtained from cells exposed to 100 nM calphostin C for 16 to 24 hours possessed predominantly 59-phosphate termini, consistent with the action of a Ca++/Mg++-dependent endonuclease. Northern and Western blot analyses revealed that the exposure to 100 nM calphostin C for 4 hours failed to alter bcl-2 transcript and protein, but exposure for more than 8 hours decreased the amount of bcl-2 transcript and protein. Together, these observations suggest that calphostin C is capable of inducing apoptotic DNA fragmentation and cell death in a highly concentration dependent manner in human glioma cells and that the apoptosis is closely associated with the decrease in transcription and translation of bcl-2.

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00

Contributor Notes

Address reprint requests to: Eiichi Tani, M.D., Department of Neurosurgery, Hyogo College of Medicine, 1–1 Mukogawa-cho, Nishinomiya, Hyogo 663, Japan.
  • 1.

    Alnemri ES, & Litwack G: Activation of internucleosomal DNA cleavage in human CEM lymphocytes by glucocorticoid and novobiocin. Evidence for a non-Ca2+-requiring mechanism(s). J Biol Chem 265:1732317333, 1990 Alnemri ES, Litwack G: Activation of internucleosomal DNA cleavage in human CEM lymphocytes by glucocorticoid and novobiocin. Evidence for a non-Ca2+-requiring mechanism(s). J Biol Chem 265:17323–17333, 1990

    • Search Google Scholar
    • Export Citation
  • 2.

    Baltuch G, , Shenouda G, & Langleben A, et al. : High dose tamoxifen in the treatment of recurrent high grade glioma: a report of clinical stabilization and tumour regression. Can J Neurol Sci 20:168170, 1993 Baltuch G, Shenouda G, Langleben A, et al: High dose tamoxifen in the treatment of recurrent high grade glioma: a report of clinical stabilization and tumour regression. Can J Neurol Sci 20:168–170, 1993

    • Search Google Scholar
    • Export Citation
  • 3.

    Baltuch GH, , Couldwell WT, & Villemure JG, et al. : Protein kinase C inhibitors suppress cell growth in established and low-passage glioma cell lines. A comparison between staurosporine and tamoxifen. Neurosurgery 33:495501, 1993 Baltuch GH, Couldwell WT, Villemure JG, et al: Protein kinase C inhibitors suppress cell growth in established and low-passage glioma cell lines. A comparison between staurosporine and tamoxifen. Neurosurgery 33:495–501, 1993

    • Search Google Scholar
    • Export Citation
  • 4.

    Barry MA, , Reynolds JE, & Eastman A: Etoposide-induced apoptosis in human HL-60 cells is associated with intracellular acidification. Cancer Res 53:23492357, 1993 Barry MA, Reynolds JE, Eastman A: Etoposide-induced apoptosis in human HL-60 cells is associated with intracellular acidification. Cancer Res 53:2349–2357, 1993

    • Search Google Scholar
    • Export Citation
  • 5.

    Basu A: The potential of protein kinase C as a target for anticancer treatment. Pharmacol Ther 59:257280, 1993 Basu A: The potential of protein kinase C as a target for anticancer treatment. Pharmacol Ther 59:257–280, 1993

    • Search Google Scholar
    • Export Citation
  • 6.

    Bates SE, , Lee JS, & Dickstein B, et al. : Differential modulation of P-glycoprotein transport by protein kinase inhibition. Biochemistry 32:91569164, 1993 Bates SE, Lee JS, Dickstein B, et al: Differential modulation of P-glycoprotein transport by protein kinase inhibition. Biochemistry 32:9156–9164, 1993

    • Search Google Scholar
    • Export Citation
  • 7.

    Bertrand R, , Solary E, & O'Connor P, et al. : Induction of a common pathway of apoptosis by staurosporine. Exp Cell Res 211:314321, 1994 Bertrand R, Solary E, O'Connor P, et al: Induction of a common pathway of apoptosis by staurosporine. Exp Cell Res 211:314–321, 1994

    • Search Google Scholar
    • Export Citation
  • 8.

    Bhalla K, , Ibrado AM, & Tourkina E, et al. : Taxol induces internucleosomal DNA fragmentation associated with programmed cell death in human myeloid leukemia cells. Leukemia 7:563568, 1993 Bhalla K, Ibrado AM, Tourkina E, et al: Taxol induces internucleosomal DNA fragmentation associated with programmed cell death in human myeloid leukemia cells. Leukemia 7:563–568, 1993

    • Search Google Scholar
    • Export Citation
  • 9.

    Bhalla K, , Tang C, & Ibrado AM, et al. : Granulocyte-macrophage colony-stimulating factor/interleukin-3 fusion protein (pIXY 321) enhances high-dose Ara-C-induced programmed cell death or apoptosis in human myeloid leukemia cells. Blood 80:28832890, 1992 Bhalla K, Tang C, Ibrado AM, et al: Granulocyte-macrophage colony-stimulating factor/interleukin-3 fusion protein (pIXY 321) enhances high-dose Ara-C-induced programmed cell death or apoptosis in human myeloid leukemia cells. Blood 80:2883–2890, 1992

    • Search Google Scholar
    • Export Citation
  • 10.

    Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248254, 1976 Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254, 1976

    • Search Google Scholar
    • Export Citation
  • 11.

    Brown DG, , Sun XM, & Cohen GM: Dexamethasone-induced apoptosis involves cleavage of DNA to large fragments prior to internucleosomal fragmentation. J Biol Chem 268:30373039, 1993 Brown DG, Sun XM, Cohen GM: Dexamethasone-induced apoptosis involves cleavage of DNA to large fragments prior to internucleosomal fragmentation. J Biol Chem 268:3037–3039, 1993

    • Search Google Scholar
    • Export Citation
  • 12.

    Collins RJ, , Harmon BV, & Gobé GC, et al. : Internucleosomal DNA cleavage should not be the sole criterion for identifying apoptosis. Int J Radiat Biol 61:451453, 1992 Collins RJ, Harmon BV, Gobé GC, et al: Internucleosomal DNA cleavage should not be the sole criterion for identifying apoptosis. Int J Radiat Biol 61:451–453, 1992

    • Search Google Scholar
    • Export Citation
  • 13.

    Cotter TG, , Lennon SV, & Glynn JM, et al. : Microfilament-disrupting agents prevent the formation of apoptotic bodies in tumor cells undergoing apoptosis. Cancer Res 52:9971005, 1992 Cotter TG, Lennon SV, Glynn JM, et al: Microfilament-disrupting agents prevent the formation of apoptotic bodies in tumor cells undergoing apoptosis. Cancer Res 52:997–1005, 1992

    • Search Google Scholar
    • Export Citation
  • 14.

    Couldwell WT, , Antel JP, & Apuzzo MLJ, et al. : Inhibition of growth of established human glioma cell lines by modulators of the protein kinase-C system. J Neurosurg 73:594600, 1990 Couldwell WT, Antel JP, Apuzzo MLJ, et al: Inhibition of growth of established human glioma cell lines by modulators of the protein kinase-C system. J Neurosurg 73:594–600, 1990

    • Search Google Scholar
    • Export Citation
  • 15.

    Couldwell WT, , Antel JP, & Yong VW: Protein kinase C activity correlates with the growth rate of malignant gliomas: Part II. Effects of glioma mitogens and modulators of protein kinase C. Neurosurgery 31:717724, 1992 Couldwell WT, Antel JP, Yong VW: Protein kinase C activity correlates with the growth rate of malignant gliomas: Part II. Effects of glioma mitogens and modulators of protein kinase C. Neurosurgery 31:717–724, 1992

    • Search Google Scholar
    • Export Citation
  • 16.

    Couldwell WT, , Gopalakrishna R, & Hinton DR, et al. : Hypericin: a potential antiglioma therapy. Neurosurgery 35:705710, 1994 Couldwell WT, Gopalakrishna R, Hinton DR, et al: Hypericin: a potential antiglioma therapy. Neurosurgery 35:705–710, 1994

    • Search Google Scholar
    • Export Citation
  • 17.

    Couldwell WT, , Hinton DR, & He S, et al. : Protein kinase C inhibitors induce apoptosis in human malignant glioma cell lines. FEBS Lett 345:4346, 1994 Couldwell WT, Hinton DR, He S, et al: Protein kinase C inhibitors induce apoptosis in human malignant glioma cell lines. FEBS Lett 345:43–46, 1994

    • Search Google Scholar
    • Export Citation
  • 18.

    Couldwell WT, , Uhm J, & Antel JP, et al. : Enhanced protein kinase C activity correlates with the growth rate of malignant gliomas in vitro. Neurosurgery 29:880887, 1991 Couldwell WT, Uhm J, Antel JP, et al: Enhanced protein kinase C activity correlates with the growth rate of malignant gliomas in vitro. Neurosurgery 29:880–887, 1991

    • Search Google Scholar
    • Export Citation
  • 19.

    Couldwell WT, , Weiss MH, & DeGiorgio CM, et al. : Clinical and radiographic response in a minority of patients with recurrent malignant gliomas treated with high-dose tamoxifen. Neurosurgery 32:485490, 1993 Couldwell WT, Weiss MH, DeGiorgio CM, et al: Clinical and radiographic response in a minority of patients with recurrent malignant gliomas treated with high-dose tamoxifen. Neurosurgery 32:485–490, 1993

    • Search Google Scholar
    • Export Citation
  • 20.

    Dekker LV, & Parker PJ: Protein kinase C—a question of specificity. Trends Biochem Sci 19:7377, 1994 Dekker LV, Parker PJ: Protein kinase C—a question of specificity. Trends Biochem Sci 19:73–77, 1994

    • Search Google Scholar
    • Export Citation
  • 21.

    DeWitte P, , Agostinis P, & Van Lint J, et al. : Inhibition of epidermal growth factor receptor tyrosine kinase activity by hypericin. Biochem Pharmacol 46:19291936, 1993 DeWitte P, Agostinis P, Van Lint J, et al: Inhibition of epidermal growth factor receptor tyrosine kinase activity by hypericin. Biochem Pharmacol 46:1929–1936, 1993

    • Search Google Scholar
    • Export Citation
  • 22.

    Falcieri E, , Martelli AM, & Bareggi R, et al. : The protein kinase C inhibitor staurosporine induces morphological changes typical of apoptosis in MOLT-4 cells without concomitant DNA fragmentation. Biochem Biophys Res Commun 193:1925, 1993 Falcieri E, Martelli AM, Bareggi R, et al: The protein kinase C inhibitor staurosporine induces morphological changes typical of apoptosis in MOLT-4 cells without concomitant DNA fragmentation. Biochem Biophys Res Commun 193:19–25, 1993

    • Search Google Scholar
    • Export Citation
  • 23.

    Forbes IJ, , Zalewski PD, & Giannakis C, et al. : Induction of apoptosis in chronic lymphoytic leukemia cells and its prevention by phorbol ester. Exp Cell Res 198:367372, 1992 Forbes IJ, Zalewski PD, Giannakis C, et al: Induction of apoptosis in chronic lymphoytic leukemia cells and its prevention by phorbol ester. Exp Cell Res 198:367–372, 1992

    • Search Google Scholar
    • Export Citation
  • 24.

    Gaido ML, & Cidlowski JA: Identification, purification, and characterization of a calcium-dependent endonuclease (NUC18) from apoptotic rat thymocytes. NUC18 is not histone H2B. J Biol Chem 266:1858018585, 1991 Gaido ML, Cidlowski JA: Identification, purification, and characterization of a calcium-dependent endonuclease (NUC18) from apoptotic rat thymocytes. NUC18 is not histone H2B. J Biol Chem 266:18580–18585, 1991

    • Search Google Scholar
    • Export Citation
  • 25.

    Gschwendt M, , Leibersperger H, & Kittstein W, et al. : Protein kinase Cζ and η in murine epidermis. TPA induces down-regulation of PKCη but not PKCζs. FEBS Lett 307:151155, 1992 Gschwendt M, Leibersperger H, Kittstein W, et al: Protein kinase Cζ and η in murine epidermis. TPA induces down-regulation of PKCη but not PKCζs. FEBS Lett 307:151–155, 1992

    • Search Google Scholar
    • Export Citation
  • 26.

    Jarvis WD, , Turner AJ, & Povirk LF, et al. : Induction of apoptotic DNA fragmentation and cell death in HL-60 human promyelocytic leukemia cells by pharmacological inhibitors of protein kinase C. Cancer Res 54:17071714, 1994 Jarvis WD, Turner AJ, Povirk LF, et al: Induction of apoptotic DNA fragmentation and cell death in HL-60 human promyelocytic leukemia cells by pharmacological inhibitors of protein kinase C. Cancer Res 54:1707–1714, 1994

    • Search Google Scholar
    • Export Citation
  • 27.

    Kerr JFR, , Winterford CM, & Harmon BV: Apoptosis. Its significance in cancer and cancer therapy. Cancer 73:20132026, 1994 Kerr JFR, Winterford CM, Harmon BV: Apoptosis. Its significance in cancer and cancer therapy. Cancer 73:2013–2026, 1994

    • Search Google Scholar
    • Export Citation
  • 28.

    Knox KA, , Finney M, & Milner AE, et al. : Second-messenger pathways involved in the regulation of survival in germinal-centre B cells and in Burkitt lymphoma lines. Int J Cancer 52:959966, 1992 Knox KA, Finney M, Milner AE, et al: Second-messenger pathways involved in the regulation of survival in germinal-centre B cells and in Burkitt lymphoma lines. Int J Cancer 52:959–966, 1992

    • Search Google Scholar
    • Export Citation
  • 29.

    Kobayashi E, , Nakano H, & Morimoto M, et al. : Calphostin C (UCN-1028C), a novel microbial compound, is a highly potent and specific inhibitor of protein kinase C. Biochem Biophys Res Commun 159:548553, 1989 Kobayashi E, Nakano H, Morimoto M, et al: Calphostin C (UCN-1028C), a novel microbial compound, is a highly potent and specific inhibitor of protein kinase C. Biochem Biophys Res Commun 159:548–553, 1989

    • Search Google Scholar
    • Export Citation
  • 30.

    Lotem J, , Cragoe EJ Jr, & Sachs L: Rescue from programmed cell death in leukemic and normal myeloid cells. Blood 78:953960, 1991 Lotem J, Cragoe EJ Jr, Sachs L: Rescue from programmed cell death in leukemic and normal myeloid cells. Blood 78:953–960, 1991

    • Search Google Scholar
    • Export Citation
  • 31.

    Lotem J, & Sachs L: Regulation by bcl-2, c-myc, and p53 of susceptibility to induction of apoptosis by heat shock and cancer chemotherapy compounds in differentiation-competent and -defective myeloid leukemia cells. Cell Growth Differ 4:4147, 1993 Lotem J, Sachs L: Regulation by bcl-2, c-myc, and p53 of susceptibility to induction of apoptosis by heat shock and cancer chemotherapy compounds in differentiation-competent and -defective myeloid leukemia cells. Cell Growth Differ 4:41–47, 1993

    • Search Google Scholar
    • Export Citation
  • 32.

    Matsumoto T, , Tani E, & Kaba K, et al. : Expression of P-glycoprotein in human glioma cell lines and surgical glioma specimens. J Neurosurg 74:460466, 1991 Matsumoto T, Tani E, Kaba K, et al: Expression of P-glycoprotein in human glioma cell lines and surgical glioma specimens. J Neurosurg 74:460–466, 1991

    • Search Google Scholar
    • Export Citation
  • 33.

    Matsumoto T, , Tani E, & Yamaura I, et al. : Effects of protein kinase C modulators on multidrug resistance in human glioma cells. Neurosurgery 36:565572, 1995 Matsumoto T, Tani E, Yamaura I, et al: Effects of protein kinase C modulators on multidrug resistance in human glioma cells. Neurosurgery 36:565–572, 1995

    • Search Google Scholar
    • Export Citation
  • 34.

    McConkey DJ, , Hartzell P, & Jondal M, et al. : Inhibition of DNA fragmentation in thymocytes and isolated thymocyte nuclei by agents that stimulate protein kinase C. J Biol Chem 264:1339913402, 1989 McConkey DJ, Hartzell P, Jondal M, et al: Inhibition of DNA fragmentation in thymocytes and isolated thymocyte nuclei by agents that stimulate protein kinase C. J Biol Chem 264:13399–13402, 1989

    • Search Google Scholar
    • Export Citation
  • 35.

    McDonnell TJ, , Troncoso P, & Brisbay SM, et al. : Expression of the protooncogene bcl-2 in the prostate and its association with the emergence of androgen-independent prostate cancer. Cancer Res 52:69406944, 1992 McDonnell TJ, Troncoso P, Brisbay SM, et al: Expression of the protooncogene bcl-2 in the prostate and its association with the emergence of androgen-independent prostate cancer. Cancer Res 52:6940–6944, 1992

    • Search Google Scholar
    • Export Citation
  • 36.

    Merep M, , Noguchi PD, & Ashwell JD: The cell cycle block and lysis of an activated T cell hybridoma are distinct processes with different Ca2+ requirements and sensitivity to cyclosporine A. J Immunol 142:40854092, 1989 Merep M, Noguchi PD, Ashwell JD: The cell cycle block and lysis of an activated T cell hybridoma are distinct processes with different Ca2+ requirements and sensitivity to cyclosporine A. J Immunol 142:4085–4092, 1989

    • Search Google Scholar
    • Export Citation
  • 37.

    Miyashita T, & Reed JC: Bcl-2 oncoprotein blocks chemotherapy-induced apoptosis in a human leukemia cell line. Blood 81:151157, 1993 Miyashita T, Reed JC: Bcl-2 oncoprotein blocks chemotherapy-induced apoptosis in a human leukemia cell line. Blood 81:151–157, 1993

    • Search Google Scholar
    • Export Citation
  • 38.

    Nakamura M, , Sakaki Y, & Watanabe N, et al. : Purification and characterization of the Ca2+ plus Mg2+-dependent endodeoxy-ribonuclease from calf thymus chromatin. J Biochem 89:143152, 1981 Nakamura M, Sakaki Y, Watanabe N, et al: Purification and characterization of the Ca2+ plus Mg2+-dependent endodeoxy-ribonuclease from calf thymus chromatin. J Biochem 89:143–152, 1981

    • Search Google Scholar
    • Export Citation
  • 39.

    Neary JT, , Norenberg LOB, & Norenberg MD: Protein kinase C in primary astrocyte cultures: cytoplasmic localization and translocation by a phorbol ester. J Neurochem 50:11791184, 1988 Neary JT, Norenberg LOB, Norenberg MD: Protein kinase C in primary astrocyte cultures: cytoplasmic localization and translocation by a phorbol ester. J Neurochem 50:1179–1184, 1988

    • Search Google Scholar
    • Export Citation
  • 40.

    Nishizuka Y: Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. Science 258:607614, 1992 Nishizuka Y: Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. Science 258:607–614, 1992

    • Search Google Scholar
    • Export Citation
  • 41.

    Nuñez G, , London L, & Hockenbery D, et al. : Deregulated bcl-2 gene expression selectively prolongs survival of growth factor-deprived hemopoietic cell lines. J Immunol 144:36023610, 1990 Nuñez G, London L, Hockenbery D, et al: Deregulated bcl-2 gene expression selectively prolongs survival of growth factor-deprived hemopoietic cell lines. J Immunol 144:3602–3610, 1990

    • Search Google Scholar
    • Export Citation
  • 42.

    Ojcius DM, , Zychlinsky A, & Zheng LM, et al. : Ionophore-induced apoptosis: role of DNA fragmentation and calcium fluxes. Exp Cell Res 197:4349, 1991 Ojcius DM, Zychlinsky A, Zheng LM, et al: Ionophore-induced apoptosis: role of DNA fragmentation and calcium fluxes. Exp Cell Res 197:43–49, 1991

    • Search Google Scholar
    • Export Citation
  • 43.

    Ojeda F, , Guarda MI, & Maldonado C, et al. : Protein kinase-C involvement in thymocyte apoptosis induced by hydrocortisone. Cell Immunol 125:535539, 1990 Ojeda F, Guarda MI, Maldonado C, et al: Protein kinase-C involvement in thymocyte apoptosis induced by hydrocortisone. Cell Immunol 125:535–539, 1990

    • Search Google Scholar
    • Export Citation
  • 44.

    Pollack IF, , Randall MS, & Kristofik MP, et al. : Response of malignant glioma cell lines to activation and inhibition of protein kinase C-mediated pathways. J Neurosurg 73:98105, 1990 Pollack IF, Randall MS, Kristofik MP, et al: Response of malignant glioma cell lines to activation and inhibition of protein kinase C-mediated pathways. J Neurosurg 73:98–105, 1990

    • Search Google Scholar
    • Export Citation
  • 45.

    Ray SD, , Kamendulis LM, & Gurule MW, et al. : Ca2+ antagonists inhibit DNA fragmentation and toxic cell death induced by acetaminophen. FASEB J 7:453463, 1993 Ray SD, Kamendulis LM, Gurule MW, et al: Ca2+ antagonists inhibit DNA fragmentation and toxic cell death induced by acetaminophen. FASEB J 7:453–463, 1993

    • Search Google Scholar
    • Export Citation
  • 46.

    Ray SD, , Sorge CL, & Kamendulis LM, et al. : Ca++-activated DNA fragmentation and dimethylnitrosamine-induced hepatic necrosis: effects of Ca++-endonuclease and poly (ADP-ribose) polymerase inhibitors in mice. J Pharmacol Exp Ther 263:387394, 1992 Ray SD, Sorge CL, Kamendulis LM, et al: Ca++-activated DNA fragmentation and dimethylnitrosamine-induced hepatic necrosis: effects of Ca++-endonuclease and poly (ADP-ribose) polymerase inhibitors in mice. J Pharmacol Exp Ther 263:387–394, 1992

    • Search Google Scholar
    • Export Citation
  • 47.

    Rosoff PM, , Stein LF, & Cantley LC: Phorbol esters induce differentiation in a pre-B-lymphocyte cell line by enhancing Na+/H+ exchange. J Biol Chem 259:70567060, 1984 Rosoff PM, Stein LF, Cantley LC: Phorbol esters induce differentiation in a pre-B-lymphocyte cell line by enhancing Na+/H+ exchange. J Biol Chem 259:7056–7060, 1984

    • Search Google Scholar
    • Export Citation
  • 48.

    Rüegg UT, & Burgess GM: Staurosporine, K-252 and UCN-01: potent but nonspecific inhibitors of protein kinases. Trends Pharmacol Sci 10:218220, 1989 Rüegg UT, Burgess GM: Staurosporine, K-252 and UCN-01: potent but nonspecific inhibitors of protein kinases. Trends Pharmacol Sci 10:218–220, 1989

    • Search Google Scholar
    • Export Citation
  • 49.

    Secrist JP, , Sehgal I, & Powis G, et al. : Preferential inhibition of the platelet-derived growth factor receptor tyrosine kinase by staurosporine. J Biol Chem 265:2039420400, 1990 Secrist JP, Sehgal I, Powis G, et al: Preferential inhibition of the platelet-derived growth factor receptor tyrosine kinase by staurosporine. J Biol Chem 265:20394–20400, 1990

    • Search Google Scholar
    • Export Citation
  • 50.

    Suzuki K, , Tadakuma T, & Kizaki H: Modulation of thymocyte apoptosis by isoproterenol and prostaglandin E2. Cell Immunol 134:235240, 1991 Suzuki K, Tadakuma T, Kizaki H: Modulation of thymocyte apoptosis by isoproterenol and prostaglandin E2. Cell Immunol 134:235–240, 1991

    • Search Google Scholar
    • Export Citation
  • 51.

    Takahashi I, , Nakanishi S, & Kobayashi E, et al. : Hypericin and pseudohypericin specifically inhibit protein kinase C: possible relation to their antiretroviral activity. Biochem Biophys Res Commun 165:12071212, 1989 Takahashi I, Nakanishi S, Kobayashi E, et al: Hypericin and pseudohypericin specifically inhibit protein kinase C: possible relation to their antiretroviral activity. Biochem Biophys Res Commun 165:1207–1212, 1989

    • Search Google Scholar
    • Export Citation
  • 52.

    Tamaoki T: Use and specificity of staurosporine, UCN-01, and calphostin C as protein kinase inhibitors. Methods Enzymol 201:340347, 1991 Tamaoki T: Use and specificity of staurosporine, UCN-01, and calphostin C as protein kinase inhibitors. Methods Enzymol 201:340–347, 1991

    • Search Google Scholar
    • Export Citation
  • 53.

    Tamaoki T, , Nomoto H, & Takahashi I, et al. : Staurosporine, a potent inhibitor of phospholipid/Ca++ dependent protein kinase. Biochem Biophys Res Commun 135:397402, 1986 Tamaoki T, Nomoto H, Takahashi I, et al: Staurosporine, a potent inhibitor of phospholipid/Ca++ dependent protein kinase. Biochem Biophys Res Commun 135:397–402, 1986

    • Search Google Scholar
    • Export Citation
  • 54.

    Vertosick FT Jr, , Selker RG, & Pollack IF, et al. : The treatment of intracranial malignant gliomas using orally administered tamoxifen therapy: preliminary results in a series of “failed” patients. Neurosurgery 30:897903, 1992 Vertosick FT Jr, Selker RG, Pollack IF, et al: The treatment of intracranial malignant gliomas using orally administered tamoxifen therapy: preliminary results in a series of “failed” patients. Neurosurgery 30:897–903, 1992

    • Search Google Scholar
    • Export Citation
  • 55.

    Walton MI, , Whysong D, & O'Connor PM, et al. : Constitutive expression of human bcl-2 modulates nitrogen mustard and camptothecin induced apoptosis. Cancer Res 53:18531861, 1993 Walton MI, Whysong D, O'Connor PM, et al: Constitutive expression of human bcl-2 modulates nitrogen mustard and camptothecin induced apoptosis. Cancer Res 53:1853–1861, 1993

    • Search Google Scholar
    • Export Citation
  • 56.

    Ways DK, , Cook PP, & Webster C, et al. : Effect of phorbol esters on protein kinase C-ζ. J Biol Chem 267:47994805, 1992 Ways DK, Cook PP, Webster C, et al: Effect of phorbol esters on protein kinase C-ζ. J Biol Chem 267:4799–4805, 1992

    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 389 73 4
Full Text Views 206 1 0
PDF Downloads 71 0 0
EPUB Downloads 0 0 0