2006 Fiscal Year Final Research Report Summary
The induction of cell death by the combination treatment with statin, lipid and derivative of steroid
| Project/Area Number |
16590131
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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 |
Medical pharmacy
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| Research Institution | Kobe Pharmaceutical University |
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Principal Investigator |
IWAKAWA Seigo Kobe Pharmaceutical University, Pharmaceutics, Professor, 薬学部, 教授 (50168548)
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| Co-Investigator(Kenkyū-buntansha) |
UEDA Kumiko Kobe Pharmaceutical University, Pharmaceutics, Lecturer, 薬学部, 講師
HIRAI Yuka Kobe Pharmaceutical University, Pharmaceutics, Instructor, 薬学部, 助手 (00289042)
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| Project Period (FY) |
2004 – 2006
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| Keywords | cancer / cell・tissue / steroid derivatives / statin / lipid |
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| Research Abstract |
We examined the combined effect of statin, lipid and a steroid derivative on the induction of cellular death in human cancer cells.
We prepared oil-in-water (O/W) lipid emulsions and studied the disposition of the emulsions. The results of the disposition study indicated that the O/W lipid emulsions prepared with n-3 polyunsaturated fatty acid-enriched triglyceride (TG) and egg-yolk lecithin were useful as drug carriers for lipophilic drugs and that O/W lipid emulsions prepared with soy oil and egg-yolk lecithin were also useful.
The effect of O/W emulsions containing n-3 polyunsaturated fatty acid-enriched TG on the survival of human breast carcinoma (MCF-7) was studied. The O/W emulsions containing eicosapentaenoic acid (EPA)-enriched TG inhibited cell growth in MCF-7. The effect of the O/W emulsions containing EPA-enriched TG was not attributable to the uptake quantity of O/W emulsions. Intracellular lipid peroxidation was suggested to contribute to the cancer cell death.
Next, we exam
… More
ined the cytotoxicity in human renal carcinoma (ACHN and ACVB) by depletion of glutathione with buthionine sulfoximine (BSO) treatment under 40% O_2. After exposure to 40% O_2, the extent of cell death was increased, compared with that under 20% O_2. We observed that treatment with 2-methoxyestradiol (2-ME), an metabolite of 17β-estradiol, under 40% O_2 showed an enhanced growth inhibition activity for ACHN and ACVB and that the combination with 2-ME and hydrogen peroxide or indometacin under 40% O_2 resulted in an increase in the intracellular reactive oxygen species (ROS) levels and showed an enhanced growth inhibition activity.
ACVB was sensitive to simvastatin compared with pravastatin for cell survival. We observed that cytotoxicity for ACVB by simvastatin was attributable to the depletion of mevalonate and geranylgeranylpyrophosphate. The inhibitory activity of docosahexaenoic acid on the survival for ACVB was suggested to be due to the combined effects of both increased intracellular H_2O_2 levels and decreased intracellular farnesylpyrophosphate and geranylgeranylpyrophosphate levels.
This study demonstrated significant combination effects of statin, lipid and derivative of steroid on the cellular death of cancer cells. Less
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