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

  • Authors:
    • 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
  • View Affiliations

  • Published online on: January 1, 2004     https://doi.org/10.3892/ijo.24.1.193
  • Pages: 193-199
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

1-β-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-β-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.

Related Articles

Journal Cover

January 2004
Volume 24 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Lee, K., Jung, Y., Hong, C., Cho, M., Bai, D., Kim, S. ... Kim, C. (2004). Activation of protein kinase C by 1-β-D-arabinofuranosylcytosine conjugates of phospholipid. International Journal of Oncology, 24, 193-199. https://doi.org/10.3892/ijo.24.1.193
MLA
Lee, K., Jung, Y., Hong, C., Cho, M., Bai, D., Kim, S., Choi, K., Yu, J., Kim, C."Activation of protein kinase C by 1-β-D-arabinofuranosylcytosine conjugates of phospholipid". International Journal of Oncology 24.1 (2004): 193-199.
Chicago
Lee, K., Jung, Y., Hong, C., Cho, M., Bai, D., Kim, S., Choi, K., Yu, J., Kim, C."Activation of protein kinase C by 1-β-D-arabinofuranosylcytosine conjugates of phospholipid". International Journal of Oncology 24, no. 1 (2004): 193-199. https://doi.org/10.3892/ijo.24.1.193