2015 Fiscal Year Research-status Report
Translational applications of broad spectrum natural compounds and phytochemicals or their derivatives to the novel treatment strategy against sarcomas
| Project/Area Number |
15K10455
|
|---|
| Research Institution | Nara Medical University |
|---|
Principal Investigator |
朴木 寛弥 奈良県立医科大学, 医学部, 准教授 (40336863)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
藤井 宏真 奈良県立医科大学, 医学部, 学内講師 (00625791)
辻内 俊文 近畿大学, 理工学部, 教授 (10254492)
藤間 保晶 奈良県立医科大学, 医学部, 研究員 (60448777)
|
|---|
| Project Period (FY) |
2015-04-01 – 2019-03-31
|
| Keywords | osteosarcoma / creatinine kinase / pterostilbene / honokiol / glucose metabolism / PI3k/Akt/mTOR / JAK/STAT |
|---|
| Outline of Annual Research Achievements |
Under our publication in ‘Seminars in Cancer Biology’ conducted with the Halifax project, we have focused on the effects of pterostilbene and honokiol as well as creatinine kinase Inhibitor against osteosarcoma cells in relation to the normal or low-glucose environment. Because cancer cells can survive under glucose-starved environment remote from blood vessels and sarcoma cells are also not exceptional, making these cells sensitive to glucose depletion with pterostilbene, honokiol and creatinine kinase inhibitor (CK-i) could potentially provide an effective intervention against them. Creatine kinase (CK) promotes resistance to glucose starvation and helps the growth and metastasis of cancer. We investigated here the effects of CKi as well as pterostilbene and honokiol on human osteosarcoma (OS) cells in different glucose conditions. Both pterostilebene and honokiol suppressed the growth of ostesarocma cells possibly would affect the pathways of PI3K/Akt/TOR as well as JAK/STAT, and glucose metabolism. Creatinine kinase inhibitor also suppressed the growth of ostesarocma cells.
|
| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
Using SaOS2 and U2OS cells, cell survival was assessed in low-glucose (L-G) and normal medium with or without CK-i., and the expression of stem cell marker of Oct-3, nestin and endoglin was examined.
CK-i treatment reduced viabilities of both cells in dose- and time-dependent manner, and L-G condition augmented those effects. In L-G condition, Oct-3 expression was increased in U2OS but reduced in SaOS2, while nestin and endoglin expressions were reduced in U2OS but increased in SaOS2. These tendencies were enhanced by CK-i.
OS cells show different response to glucose condition and CK-i, suggesting the difference in the kinetics of glucose metabolism is possibly dependent on differentiation stages.
Pterostilebene and honokiol suppressed the growth of ostesarocma cells in dose- and time-dependent manner possibly would affect the pathways of PI3K/Akt and mTOR, and glucose metabolism.
|
| Strategy for Future Research Activity |
We will conduct the investigation of the effects of pterostilbene and honokiol, and possibly the combination of both agents in low-glucose environment against osteosarcoma cell. The pathways involved in the effects of these agents are will also be investigated focusing on PI3K/Akt/mTOR and JAK/STAT pathways. Glucose metabolism pathways are also investigated in the experiments of the treatment of these agents in conjunction with different glucose condition.
We will also focusing on the effects of these treatments in terms of the stemness characteristics such as sphere forming ability in 3D culture system as well as stem cell markers.
We will apply these agents into in vivo with the rat osteosarcoma model in the final stage of this research project.
|
| Causes of Carryover |
We have planed the gene expression analysis using cDNA Plate Arrays with cells treated by pterostilebene and honokiol. Due to the requirement of deep consideration for selection of the plates (i.e. pathway selection), we will this analysis in the next experiment term.
|
| Expenditure Plan for Carryover Budget |
We will conduct the experiments with cDNA Plate Array and the results of the analysis will apply for further detailed genetic alteration analysis.
|
Research Products
(19 results)
