1998 Fiscal Year Final Research Report Summary
Molecular design and synthesis of anti-cancer compounds that cause apoptosis
| Project/Area Number |
09672280
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
医薬分子機能学
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| Research Institution | Kumamoto University |
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Principal Investigator |
OTSUKA Masami Kumamoto University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (40126008)
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| Project Period (FY) |
1997 – 1998
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| Keywords | apoptosis / apoptosis resistant cell / active oxygen / anti-cancer agent |
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| Research Abstract |
Apoptosis is a programmed cell death induced through the intracellular signalling pathway caused by the binding of TNF or Fas ligand with receptors of cell surface. Involvement of active oxygen species has been postdated in the signal transduction pathway leading to apoptosis. The objective of the present research is to synthesize man-made molecules that supply active oxygen into the signalling pathway to induce apoptosis in the tumor cells.
The head investigators are successful in the synthesis of highly efficient oxygen activating molecules by introducing various functional groups such as imidazole into dimethylaminopyridine. The synthesitic molecule induced apoptosis in mouse leukaemia L1210 cells, human leukaemia K562/ADM cells, human carcinoma KB-C4 cells, and human pancreatic carcinoma AsPC-1 cells depending on time and concentration. The cell death was found to be apoptosisbased on the morphological change of the cells and intranucleosomal degradation of DNA.
The apoptosis was inhibited by an antioxidant ascorbic acid suggesting the involvement of active oxygen species. It was found that caspase-1, caspase-3, Bcl-2, Bax, p53, and p21 do not participate in the apoptosis caused by the synthetic molecule.
Thus the head investigators are successful in the molecular design and synthesis of an artificial molecule that generates active oxygen species to induce apoptosis in carcinoma cells.
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