Valproic acid exerts anti-tumor as well as anti-angiogenic effects on myeloma
| العنوان: | Valproic acid exerts anti-tumor as well as anti-angiogenic effects on myeloma |
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| المؤلفون: | Ayako Nakano, Shuji Ozaki, Takeshi Harada, Hiroe Amou, Toshio Matsumoto, Masahiro Abe, Kenichi Kitazoe, Asuka Oda, Toshihiro Hashimoto, Masahiro Hiasa, Kyoko Takeuchi |
| المصدر: | International Journal of Hematology. 89:45-57 |
| بيانات النشر: | Springer Science and Business Media LLC, 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Melphalan, medicine.medical_specialty, Cell Survival, medicine.drug_class, Angiogenesis, Osteoclasts, Biology, Bone Marrow, immune system diseases, hemic and lymphatic diseases, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Tumor Cells, Cultured, medicine, Humans, Multiple myeloma, Cell Proliferation, Hematology, Valproic Acid, Histone deacetylase inhibitor, Drug Synergism, medicine.disease, Coculture Techniques, Thalidomide, Histone Deacetylase Inhibitors, medicine.anatomical_structure, Apoptosis, Cancer research, lipids (amino acids, peptides, and proteins), Bone marrow, Multiple Myeloma, medicine.drug |
| الوصف: | Multiple myeloma is still an incurable disease, most commonly occurring in the elderly. The myeloma-induced bone marrow microenvironment protects myeloma cells from drug-induced apoptosis. Therefore, the development of novel and tolerable therapeutic alternatives to overcome the drug resistance is an important clinical issue. Valproic acid (VPA), a safe and widely used anti-epileptic agent, is revisited as a class I- and IIa-specific histone deacetylase inhibitor. In the present study, we evaluated the effect as well as a mechanism of actions of VPA on myeloma cell growth and survival, with special reference to the myeloma-induced bone marrow microenvironment. VPA at therapeutic concentrations for epilepsy induced cell death in primary CD138-positive myeloma cells as well as myeloma cell lines, but not in CD138-negative bone marrow cells. VPA suppressed osteoclastogenesis as well as osteoclast-mediated myeloma cell growth. VPA also inhibited vascular tubule formation enhanced by co-cultures of myeloma cells and osteoclasts in concert with thalidomide. In addition, VPA induced both caspase-dependent and -independent cell death in myeloma cells, and potentiated the anti-myeloma effects of melphalan and dexamethasone. Collectively, VPA is suggested to exert multi-factorial anti-myeloma actions, and may serve as a safe adjuvant to be included in conventional chemotherapies against myeloma. |
| تدمد: | 1865-3774 0925-5710 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e8156494622b48230176389b36c69dfa https://doi.org/10.1007/s12185-008-0226-9 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....e8156494622b48230176389b36c69dfa |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 18653774 09255710 |
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