ABSTRACT
Curcumin is the pigment of turmeric and has been reported as a signal transduction modulator and inhibitor of transcription factors, for example, NF-kappaB. In our article we found a concentration-dependent cytotoxic activity of curcumin in a panel of eight leukemic cell lines (SKW-3, CEM, U-937, HL-60, HL-60/Dox, K-562, LAMA-84, and AR-230). Additive to synergistic interactions was recorded for combinations with bendamustine and idarubicine in SKW-3 and LAMA-84 cells. Noteworthy, in multiple myeloma cells (RPMI-8226 and U-266) a potentiation of the efficacy of bendamustine by curcumin application was found. Moreover, curcumin increased the bendamustine cytotoxicity in cultures of cells isolated from the bone marrow of a patient with non-Hodgkin's lymphoma (NHL). The increased bendamustine efficacy could be explained by NF-kappaB inhibition, because this factor is activated in many cancers, especially leukemia and multiple myeloma. Curcumin is characterized by low toxicity and was described to have a chemoprotective activity. Therefore, the level of reduced glutathione (GSH) was measured and a concentration-dependent increase of GSH levels was recorded in AR-230 and SKW-3 cells (concentration range 5-25 muM). Experiments with mice showed significant protection against cisplatin-induced chromosomal aberrations (clastogenic effect) and inhibition of mitoses in bone marrow cells. Curcumin alone caused reduction of the mitotic index. In combination with cisplatin, however, this parameter was increased when compared to cisplatin alone. Our data indicate that curcumin has pleiotropic effects on signal transduction by inhibiting transcription thus exerting antitumor activity. In addition, curcumin has protective and anticlastogenic activity by enhancing the scavenging of free radicals.
