Cancer Chemotherapy and Pharmacology

, Volume 33, Issue 4, pp 273–280 | Cite as

Effect of UCN-01, a selective inhibitor of protein kinase C, on the cell-cycle distribution of human epidermoid carcinoma, A431 cells

  • Shiro Akinaga
  • Kayo Nomura
  • Katsushige Gomi
  • Masami Okabe
Original Articles Protein Kinase C, Cell Cycle, Staurosporine, Human Epidemoid Carcinoma
Received:
Accepted:

Abstract

UCN-01 (7-hydroxy-staurosporine), a selective inhibitor of protein kinase C (PKC), was shown to exhibit antitumor activity in murine and human tumor cell lines in vitro and in vivo. On the other hand, staurosporine, a nonselective protein kinase inhibitor, was not shown to exert antitumor activity in vivo despite its potent antiproliferative activity in vitro. To compare the modes of action of UCN-01 and staurosporine in vitro, the effects of both drugs on the cell cycle progression of human epidermoid carcinoma A431 cells were examined by flow cytometry using propidium iodide (PI) staining. At 50% growth inhibitory concentrations, both UCN-01 and staurosporine induced G1 phase accumulation in the cell cycle. At 80% growth inhibitory concentrations, UCN-01 also induced preferential G1 phase accumulation, but staurosporine mostly induced G2M phase accumulation. Staurosporine also induced higher DNA ploidy when the cells were exposed to the drug for more than one generation time of A431 cells. An analysis of cell kinetics by 5-bromo-2-deoxyuridine incorporation versus DNA content confirmed that the G1 phase block by UCN-01 and the G1 and G2M phase block by staurosporine at the respective doses, as was the case for PI staining. Additionally, DNA synthesis of the cells, which was determined by the uptake of3H-TdR, was not suppressed at least 8 h after the treatment with UCN-01. These results suggested that UCN-01 could affect the G1 phase of cell cycle in A431 cells in quite different manners from staurosporine. The G1 phase block induced by UCN-01 might be important for the growth inhibitory activity of UCN-01 against A431 cells in vitro and in vivo.

Keywords

A431 Cell Propidium Iodide Staurosporine Human Epidermoid Carcinoma Carcinoma A431 Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations used

PKC

Ca2+ and phospholipid-dependent serine/threonine kinase

PBS

phosphate buffered saline

PI

propidium iodide

FITC

fluorescein isothiocyanate

cPKC

conventional PKC including

PKC α

β and γ

nPKC

neo PKC including PKC δ, ε, η (L) and θ

IC50

concentration required for 50% growth inhibition

IPA

phorbol 12-myristate 13-acetate

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Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • Shiro Akinaga
    • 1
  • Kayo Nomura
    • 1
  • Katsushige Gomi
    • 1
  • Masami Okabe
    • 1
  1. 1.Pharmaceutical Research LaboratoriesKyowa Hakko Kogyo Co., Ltd.Shizuoka-kenJapan

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