| Budget Amount *help |
¥34,580,000 (Direct Cost: ¥26,600,000、Indirect Cost: ¥7,980,000)
Fiscal Year 2015: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Fiscal Year 2014: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Fiscal Year 2013: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2012: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
Fiscal Year 2011: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
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| Outline of Final Research Achievements |
Protein kinase C (PKC) isozymes play central roles in the signal transduction on the cell surface and could serve as promising therapeutic targets of intractable diseases like cancer and Alzheimer's disease. Although natural PKC ligands like phorbol esters have the potential to become therapeutic leads, most of them are potent tumor promoters and proinflammatory on mouse skin. We focused on the skeleton of aplysiatoxin (ATX), a natural PKC ligand isolated from sea hare. We found 10-methyl-aplog-1, a simplified analog of ATX, to have strong anti-proliferative activity against several cancer cell lines with little tumor-promoting and inflammatory activities. In order to examine the anti-cancer activity in vivo and mechanism of action, several hundred milligrams of 10-methyl-aplog-1 was synthesized. 10-Methyl-aplog-1 exhibited significant anti-cancer activity against mouse xenograft models, and its anti-proliferative activity derived in part from activation of protein kinase C α.
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