Activation of protein kinase C by 1-beta-D-arabinofuranosylcytosine conjugates of phospholipid.

Kee Ho Lee, Yu Jin Jung, Chung Il Hong, Myung Haing Cho, Dong Hoon Bai, Sang Hoon Kim, Kang-Yell Choi, Ju Hyun Yu, Chang Min Kim

Research output: Contribution to journalArticle

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Abstract

1-beta-D-arabinofuranosylcytosine (ara-C) conjugates of phospholipid were shown to be highly antineoplastic against various tumor cells. In this study, we report that these conjugates are potent activators of protein kinase C (PKC, EC) in vitro. Although required Ca2+, PKC activation by the conjugates occurred even in the absence of phospholipid and diacylglycerol. Among the conjugates, 1-beta-D-arabino-furanosylcytosine 5'-diphosphate-rac-1-O-octadecyl-2-O-palmitoylglycerol [(ara-CDP-DL-PBA); ara-C conjugate of ether phospholipid], was employed to investigate its mode of activation, since ether phospholipid has been reported to be a regulator of the PKC. When PKC was activated by ara-CDP-DL-PBA, diacylglycerol enhanced its activity with 3-fold reduction of an apparent Ka value for ara-CDP-DL-PBA and no change in the Vmax. During the PKC activation by phosphatidylserine, ara-CDP-DL-PBA exhibited a synergistic effect on the activation. Studies on the relationship between the structures of ara-CDP-DL-PBA and their effects on PKC activity showed that phosphate group of ether lipid was important for its activation of PKC, and that conjugation of ara-C and ether lipid further enhanced the enzyme activity. These results suggest that the ara-C conjugate of phospholipid activates PKC in a co-operative manner with diacylglycerol and/or phosphatidylserine, however, the exact mechanism of the antineoplastic effect of ara-CDP-DL-PBA through PKC activation still remains speculative.

Original languageEnglish
Pages (from-to)193-199
Number of pages7
JournalInternational journal of oncology
Volume24
Issue number1
Publication statusPublished - 2004 Jan 1

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Protein Kinase C beta
Cytidine Diphosphate
Cytarabine
Phospholipids
Diglycerides
Phospholipid Ethers
Phosphatidylserines
Antineoplastic Agents
Ether
Lipids
Diphosphates
Protein Kinase C
Phosphates
Enzymes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Lee, K. H., Jung, Y. J., Hong, C. I., Cho, M. H., Bai, D. H., Kim, S. H., ... Kim, C. M. (2004). Activation of protein kinase C by 1-beta-D-arabinofuranosylcytosine conjugates of phospholipid. International journal of oncology, 24(1), 193-199.
Lee, Kee Ho ; Jung, Yu Jin ; Hong, Chung Il ; Cho, Myung Haing ; Bai, Dong Hoon ; Kim, Sang Hoon ; Choi, Kang-Yell ; Yu, Ju Hyun ; Kim, Chang Min. / Activation of protein kinase C by 1-beta-D-arabinofuranosylcytosine conjugates of phospholipid. In: International journal of oncology. 2004 ; Vol. 24, No. 1. pp. 193-199.
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title = "Activation of protein kinase C by 1-beta-D-arabinofuranosylcytosine conjugates of phospholipid.",
abstract = "1-beta-D-arabinofuranosylcytosine (ara-C) conjugates of phospholipid were shown to be highly antineoplastic against various tumor cells. In this study, we report that these conjugates are potent activators of protein kinase C (PKC, EC) in vitro. Although required Ca2+, PKC activation by the conjugates occurred even in the absence of phospholipid and diacylglycerol. Among the conjugates, 1-beta-D-arabino-furanosylcytosine 5'-diphosphate-rac-1-O-octadecyl-2-O-palmitoylglycerol [(ara-CDP-DL-PBA); ara-C conjugate of ether phospholipid], was employed to investigate its mode of activation, since ether phospholipid has been reported to be a regulator of the PKC. When PKC was activated by ara-CDP-DL-PBA, diacylglycerol enhanced its activity with 3-fold reduction of an apparent Ka value for ara-CDP-DL-PBA and no change in the Vmax. During the PKC activation by phosphatidylserine, ara-CDP-DL-PBA exhibited a synergistic effect on the activation. Studies on the relationship between the structures of ara-CDP-DL-PBA and their effects on PKC activity showed that phosphate group of ether lipid was important for its activation of PKC, and that conjugation of ara-C and ether lipid further enhanced the enzyme activity. These results suggest that the ara-C conjugate of phospholipid activates PKC in a co-operative manner with diacylglycerol and/or phosphatidylserine, however, the exact mechanism of the antineoplastic effect of ara-CDP-DL-PBA through PKC activation still remains speculative.",
author = "Lee, {Kee Ho} and Jung, {Yu Jin} and Hong, {Chung Il} and Cho, {Myung Haing} and Bai, {Dong Hoon} and Kim, {Sang Hoon} and Kang-Yell Choi and Yu, {Ju Hyun} and Kim, {Chang Min}",
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Lee, KH, Jung, YJ, Hong, CI, Cho, MH, Bai, DH, Kim, SH, Choi, K-Y, Yu, JH & Kim, CM 2004, 'Activation of protein kinase C by 1-beta-D-arabinofuranosylcytosine conjugates of phospholipid.', International journal of oncology, vol. 24, no. 1, pp. 193-199.

Activation of protein kinase C by 1-beta-D-arabinofuranosylcytosine conjugates of phospholipid. / Lee, Kee Ho; Jung, Yu Jin; Hong, Chung Il; Cho, Myung Haing; Bai, Dong Hoon; Kim, Sang Hoon; Choi, Kang-Yell; Yu, Ju Hyun; Kim, Chang Min.

In: International journal of oncology, Vol. 24, No. 1, 01.01.2004, p. 193-199.

Research output: Contribution to journalArticle

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T1 - Activation of protein kinase C by 1-beta-D-arabinofuranosylcytosine conjugates of phospholipid.

AU - Lee, Kee Ho

AU - Jung, Yu Jin

AU - Hong, Chung Il

AU - Cho, Myung Haing

AU - Bai, Dong Hoon

AU - Kim, Sang Hoon

AU - Choi, Kang-Yell

AU - Yu, Ju Hyun

AU - Kim, Chang Min

PY - 2004/1/1

Y1 - 2004/1/1

N2 - 1-beta-D-arabinofuranosylcytosine (ara-C) conjugates of phospholipid were shown to be highly antineoplastic against various tumor cells. In this study, we report that these conjugates are potent activators of protein kinase C (PKC, EC) in vitro. Although required Ca2+, PKC activation by the conjugates occurred even in the absence of phospholipid and diacylglycerol. Among the conjugates, 1-beta-D-arabino-furanosylcytosine 5'-diphosphate-rac-1-O-octadecyl-2-O-palmitoylglycerol [(ara-CDP-DL-PBA); ara-C conjugate of ether phospholipid], was employed to investigate its mode of activation, since ether phospholipid has been reported to be a regulator of the PKC. When PKC was activated by ara-CDP-DL-PBA, diacylglycerol enhanced its activity with 3-fold reduction of an apparent Ka value for ara-CDP-DL-PBA and no change in the Vmax. During the PKC activation by phosphatidylserine, ara-CDP-DL-PBA exhibited a synergistic effect on the activation. Studies on the relationship between the structures of ara-CDP-DL-PBA and their effects on PKC activity showed that phosphate group of ether lipid was important for its activation of PKC, and that conjugation of ara-C and ether lipid further enhanced the enzyme activity. These results suggest that the ara-C conjugate of phospholipid activates PKC in a co-operative manner with diacylglycerol and/or phosphatidylserine, however, the exact mechanism of the antineoplastic effect of ara-CDP-DL-PBA through PKC activation still remains speculative.

AB - 1-beta-D-arabinofuranosylcytosine (ara-C) conjugates of phospholipid were shown to be highly antineoplastic against various tumor cells. In this study, we report that these conjugates are potent activators of protein kinase C (PKC, EC) in vitro. Although required Ca2+, PKC activation by the conjugates occurred even in the absence of phospholipid and diacylglycerol. Among the conjugates, 1-beta-D-arabino-furanosylcytosine 5'-diphosphate-rac-1-O-octadecyl-2-O-palmitoylglycerol [(ara-CDP-DL-PBA); ara-C conjugate of ether phospholipid], was employed to investigate its mode of activation, since ether phospholipid has been reported to be a regulator of the PKC. When PKC was activated by ara-CDP-DL-PBA, diacylglycerol enhanced its activity with 3-fold reduction of an apparent Ka value for ara-CDP-DL-PBA and no change in the Vmax. During the PKC activation by phosphatidylserine, ara-CDP-DL-PBA exhibited a synergistic effect on the activation. Studies on the relationship between the structures of ara-CDP-DL-PBA and their effects on PKC activity showed that phosphate group of ether lipid was important for its activation of PKC, and that conjugation of ara-C and ether lipid further enhanced the enzyme activity. These results suggest that the ara-C conjugate of phospholipid activates PKC in a co-operative manner with diacylglycerol and/or phosphatidylserine, however, the exact mechanism of the antineoplastic effect of ara-CDP-DL-PBA through PKC activation still remains speculative.

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