Cucurbitacin B induces cell cycle arrest, apoptosis and autophagy associated with G actin reduction and persistent activation of cofilin in Jurkat cells.
Pharmacology. 2012 ;89(5-6):348-6. PMID: 22699368
AIM: The present study aimed to explore the antitumor effect and action mechanism of cucurbitacin B (CuB) on human T-cell leukemia Jurkat cells.
METHODS: Cell proliferation was measured by the MTS assay. Cell cycle distribution, mitochondrial membrane potential and annexin V staining were analyzed using flow cytometry. Western blotting was used to determine the levels of apoptosis- and autophagy-related proteins.
RESULTS: CuB inhibited the proliferation of Jurkat cells in a dose-dependent manner and induced G 2 /M phase arrest as well as formation of tetraploid cells. Accompanied with these effects, the actin dynamics was disrupted, and cofilin, a key regulator of actin dynamics, was persistently activated (dephosphorylated). Although CuB induced around 10% cells undergoing apoptosis, most of the cells were alive after CuB treatment for 24 h. Induction of autophagy was also evident by accumulation of LC3-II. CuB-induced autophagy seemed to be a prosurvival response, since suppression of CuB-induced autophagy significantly increased the activation of caspase-3.
CONCLUSION: Our results demonstrated that CuB exhibited antitumor activity in Jurkat cells through induction of cell cycle arrest and apoptosis which was at least partly due to the disruption of actin dynamics.