Abstract
Supernumerary centrosomes and aneuploidy are associated with a malignant phenotype
of tumor cells. Centrosomal clustering is a mechanism used by cancer cells with supernumerary
centrosomes to solve the threatening problem of multipolar spindles. Griseofulvin
is an antifungal substance that interferes with the microtubule apparatus and inhibits
centrosomal clustering. It has also been demonstrated that griseofulvin inhibits the
growth of tumor cells in vitro and in vivo. However, it is not yet known whether treatment
with griseofulvin inhibits growth of adrenocortical tumor cells. We studied the viability
and antiproliferative effects of griseofulvin on cultured NCI-H295R adrenocortical
carcinoma cells using Wst-1-, BrdUrd-, and [3H]-thymidine assays. For the detection of apoptosis we used a caspase 3/7 cleavage
assay and light microscopy techniques. We observed that incubation with griseofulvin
for 24–48 h leads to a decrease in the viability and proliferation of NCI-H295R cells
in a dose-dependent manner. Significant effects could be observed after incubation
with griseofulvin as measured by Wst-1-, BrdUrd-, and [3H]dT- uptake assays. Apoptosis of NCI-H295R cells was increased in a dose-dependent
manner up to 4.5-fold after incubation with griseofulvin 40 μM for 24 h as shown by
caspase 3/7 cleavage assay and light microscopy. With regard to new treatment strategies
for adrenocortical cancer, griseofulvin, and possibly other agents, which interfere
with the microtubule apparatus and inhibit centrosomal clustering, may turn out to
be interesting targets for further research.
Key words
adrenal tumor - proliferation - viability - apoptosis
