Synergistic growth inhibition of YM529 with biologic response modifiers (BRMs) in myeloma cells

• Published in: International journal of hematology Vol. 75; no. 5; pp. 534 - 539
• Main Authors: YATA, Kenichiro, OTSUKI, Takemi, YAMADA, Osamu, WADA, Hideho, YAWATA, Yoshihito, SUGIHARA, Takashi
• Format: Journal Article
• Language: English
• Published: Tokyo Springer 01.06.2002; Springer Nature B.V
• Subjects: Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Biological and medical sciences; Cell Division - drug effects; Chemotherapy; Diphosphonates - pharmacology; Drug Synergism; Humans; Imidazoles - pharmacology; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Interferon-alpha - pharmacology; Interphase - drug effects; Medical sciences; Multiple Myeloma - drug therapy; Multiple Myeloma - pathology; Pharmacology. Drug treatments; RNA - drug effects; Thalidomide - pharmacology; Tretinoin - pharmacology; Tumor Cells, Cultured - drug effects; Antineoplastic agent; Human; Cell proliferation; Immunopathology; Alpha interferon; Cytokine; Retinoid; Malignant hemopathy; Cell differentiation; Myeloma; Bisphosphonates; In vitro; Biological activity; Immunoglobulinopathy; Lymphoproliferative syndrome; Established cell line; Thalidomide; Tumor cell; Apoptosis; Tretinoin
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/BF02982119

Bisphosphonates (BPs) are effective in the management of bone disease in patients with multiple myeloma. Recent reports have suggested that they may also have an antitumor activity. YM529 is a new synthetic BP with more than 1000 times the bone resorption inhibitory activity of pamidronate. To clarify the direct effects of YM529 on myeloma cells, the cell proliferation and cell cycle perturbation were analyzed using 12 myeloma cell lines established in our laboratory. The growth inhibition was dose dependent. The cells accumulated in [2n<<4n] of the cell cycle and subsequently formed an apoptotic sub-G1 fraction. Combined treatment with all-trans retinoic acid, thalidomide, or interferon-alpha enhanced the growth inhibitory effects of YM529 on these cells. However, there were no remarkable effects of YM529 on the messenger RNA expression for angiogenic factors, cell cycle regulators, or cytokines related to myeloma cells. These results indicate that YM529 is beneficial not only to bone lesions but also for its direct antitumor effects on myeloma cells.