griseofulvin and Multiple-Myeloma

Recent innovations in the development of systemic and targeted therapies have improved survival and quality of life in multiple myeloma (MM) patients. However, in most cases, this hematological malignancy of monoclonal B-lymphocytes remains incurable. Exaggerated Wnt/β-catenin signaling has been demonstrated in lymphoma and MM, therefore targeting related signaling molecules might represent a promising therapy approach. Griseofulvin, a widely used antifungal drug, is chemically related to other known Wnt-inhibitors and we recently demonstrated its potent in vivo efficacy in a murine myeloma model.. The anti-tumor apoptotic effect of griseofulvin at doses ranging from 0.1-200 μM was investigated on a total of ten human and two murine myeloma/lymphoma cell lines, as determined by 3'3-dihexyloxacarbocyanine iodide (DiOC6) and propidium iodide (PI) staining in flow cytometry.. Griseofulvin significantly induced apoptosis in all investigated myeloma and lymphoma cell lines in a dose-dependent manner, while healthy control cells were less sensitive.. Given the known safety profile and apoptosis induction at low effective doses, our data warrant further in vitro and in vivo studies utilizing griseofulvin as a potential therapy agent for MM and lymphoma.

Topics: Animals; Antifungal Agents; Antineoplastic Agents; Apoptosis; Cell Line; Cell Line, Tumor; Cell Survival; Cells, Cultured; Griseofulvin; Humans; Lymphocytes; Lymphoma; Mice; Multiple Myeloma

We recently confirmed that ciclopirox olamine inhibits Wnt/beta catenin signalling in myeloma. Griseofulvin (GF) has similar chemical features as compared to ciclopirox olamine. In this study the anti-tumor effect of GF was investigated. GF demonstrated a major apoptotic activity in various human and murine myeloma and lymphoma cell lines as well as in human primary cells. In vivo, tumor growth as well as overall survival were significantly reduced in mice treated with GF as compared to untreated mice. In conclusion, our results reveal a significant selective induction of apoptosis by GF and suggest a significant in vivo effect against myeloma.

Topics: Animals; Antifungal Agents; Antineoplastic Agents; Apoptosis; beta Catenin; Cell Line, Tumor; Ciclopirox; Griseofulvin; Humans; Immunosuppressive Agents; Lenalidomide; Lymphoma; Mice; Mice, Inbred BALB C; Multiple Myeloma; Pyridones; Signal Transduction; Survival Rate; Thalidomide; Treatment Outcome