1999 Fiscal Year Final Research Report Summary
Investigation of natural products with selective cytotoxicity against tumor cells
| Project/Area Number |
10470472
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Chemical pharmacy
|
|---|
| Research Institution | Nagoya City University |
|---|
Principal Investigator |
OGIHARA Yukio Nagoya City Univ., Pharmacognosy, Prof., 薬学部, 教授 (70080166)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KOJIMA Keisuke Nagoya City Univ., Pharmacognosy, Assistant Prof., 薬学部, 助手 (40275144)
NOSE Mitsuhiko Nagoya City Univ., Pharmacognosy, Lecturer, 薬学部, 講師 (60228327)
INOUE Makoto Nagoya City Univ., Pharmacognosy, Associate Prof., 薬学部, 助教授 (50191888)
|
|---|
| Project Period (FY) |
1998 – 1999
|
| Keywords | Gallic Acid / Zephyranthes alkaloids / Apoptosis / Selectivity / FK506 binding protein 12 / Peptidyl-prolyl cis-trans isomerase / Histone H3 |
|---|
| Research Abstract |
In this study, the mechanism by which natural products, gallic acid and Zephyranthes alkaloids, show selective cytotoxicity against tumor cells relative to normal cells was investigated. In apoptosis induced by gallic acid, some proteins increased after gallic acid treatment. Among them, N-terminal amino acid sequences of three proteins were determined and were found to have high homology with FK506 binding protein 12 (FKBP12), peptidyl-prolyl cis-trans isomerase (Pin-1), and histone H3. Furthermore, mRNA levels of FKBP12 and Pin-1 was elevated, thus indicating that these two proteins should be synthesized after gallic acid treatment. Further study indicated that gallic acid first generated reactive oxygen species and then increased intracellular CaィイD1++ィエD1, followed by increase of FKBP12, Pin-1 and histone H3. The pricise mechanism of these three proteins in gallic acid-induced apoptosis remained to be determined.
1-(3-Hydroxybutylyl)pancratistatin (HBP) and 1-((S)-(+)-3-beta-D-glucopyranosyloxybutylyl) pancratistatin (GBP) were isolated from Zephyranthes carinata and was found to induce apoptosis in tumor cells. GBP inhibited cell growth at G0/G1 and G2/M phases. On the other hand, HBP prevented cell growth at G0/G1, S, and G2/M phases. That is, both compounds influenced the machinery of cell cycle to result in inhibition of cell growth and apoptosis induction.
|
