Cucurbitacin B induces cell cycle arrest, apoptosis and autophagy associated with G actin reduction and persistent activation of cofilin in Jurkat cells.
OBJECTIVE
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.


CONCLUSIONS
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.
Department of Immunobiology, Jinan University, Guangzhou, PR China.
Jun-Shan
JS
Zhu
Dong-Yun
DY
Ouyang
Zhi-Jian
ZJ
Shi
Li-Hui
LH
Xu
Yan-Ting
YT
Zhang
Xian-Hui
XH
He
D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D019169:Jurkat Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D014315:Triterpenes / Q000494:pharmacology*
D051339:Actin Depolymerizing Factors; D000199:Actins; D000970:Antineoplastic Agents; D014315:Triterpenes; C041246:cucurbitacin B; D053148:Caspase 3