COMPARATIVE STUDIES ON THE COMBINED CYTOTOXIC EFFECT OF FORSKOLIN WITH MITOMYCIN C AND RESPONSIVENESS TO FORSKOLIN IN RAT ASCITES HEPATOMA AH66 CELLS AND AH66F CELLS

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概要

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• The combined cytotoxic effect of forskolin with mitomycin C (MMC) was investigated using two cell lines, AH66 and AH66F. Forskolin significantly enhanced the cytotoxicity of MMC and increased the uptake of MMC and the intracellular adenosine 3', 5'-cyclic monophosphate (cyclic AMP) level in AH66 cells but similar results were not obtained with AH66F cells. Dibutyryl cyclic AMP enhanced the effect and uptake of MMC in both cell lines. These results confirm that elevated cyclic AMP in the cells increases the cellular uptake of MMC and enhances the cytotoxicity of MMC as reported in our previous papers. Therefore, forskolin may be suitable for antitumor combination therapy. On the other hand, the functional components associated with the cyclic AMP generating system were thought to be present in membranes of both AH66 cells and AH66F cells from results that showed that cholera toxin, islet-activating protein and prostaglandin E_1 increased the level of cyclic AMP in both cells. The elevation of cyclic AMP by these adenylate cyclase activators in AH66 cells was augmented by forskolin. However, the cyclic AMP level in AH66F cells was scarcely affected by forskolin and the elevation of cyclic AMP by the activators was inhibited by this diterpene. From these results, it appears that the AH66F cell line may be useful for the elucidation of the action mechanism of forskolin and of the transmission system from hormone receptors to adenylate cyclase.

• 公益社団法人日本薬学会の論文

著者

• Takagi K

  Department Of Medical Technology Nagoya University School Of Health Sciences

• Kondo Takaaki

  Department Of Cardiology Nagoya University Graduate School Of Medicine

• MIYAMOTO Kenichi

  Department of Medical Genetics, Ehime University School of Medicine

• HASEGAWA Takaaki

  Department of Pharmacy and Pharmacokinetics, Aichi Medical University School of Medicine

• Satake Tatsuo

  Second Department of Internal Medicine, Nagoya university School of Medicine, Nagoya

• Satake Tatsuo

  Third Division Of The Research Laboratory For Development Of Medicine School Of Pharmacy Hokuriku Un

• TAKAGI Kenzo

  Second Department of Internal Medicine

• MIYAMOTO Kenichi

  Research Laboratory for Development of Medicine, School of Pharmacy, Hokuriku University

• Kawaguchi Takeshi

  Kyoto University Center For Student Health

• Miyamoto Kenichi

  Department Of Hospital Pharmacy And Department Of Medicinal Informatics Graduate School Of Medical S

• Matsunaga Takayuki

  Third Division Of The Research Laboratory For Development Of Medicine School Of Pharmacy Hokuriku Un

• Hasegawa Takaaki

  Department Of Pharmacy And Pharmacokinetics Aichi Medical University School Of Medicine

• Hasegawa Takaaki

  Third Division Of The Research Laboratory For Development Of Medicine School Of Pharmacy Hokuriku Un

• Koshiura Ryozo

  Third Division Of Research Department Research Laboratory For Development Of Medicine School Of Phar

• MATSUNAGA TAKAYUKI

  Department of Pharmacology, Hokuriku University School of Pharmacy

• KOSHIURA RYOZO

  Department of Pharmacology, Hokuriku University School of Pharmacy

• Miyamoto K

  Department Of Medical Informatics Graduate School Of Medical Science Kanazawa University

• Koshiura R

  Third Division Of Research Department Research Laboratory For Development Of Medicine School Of Phar

• Miyamoto K

  Department Of Engineering Physics And Mechanics Kyoto University

• Hasegawa Takaaki

  Department Of Hospital Pharmacy Nagoya University School Of Medicine

• Miyamoto Kenichi

  Department Of Chemistry For Materials Faculty Of Engineering And Graduate School Of Engineering Mie

• SATAKE Tatsuo

  Second Department of Internal Medicine, Nagoya University School of Medicine

• MIYAMOTO Kenichi

  Department of Engineering Physics and Mechanics, Kyoto University

• HASEGAWA Takaaki

  Department of Bacteriology, Nagoya University School of Medicine

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