Open AccessAurora A selective inhibitor MLN8237 suppresses the growth and survival of HTLV‐1‐infected T‐cells in vitro
Author(s) -
Tomita Mariko,
Mori Naoki
Publication year - 2010
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2010.01499.x
Subject(s) - in vitro , growth inhibition , biology , virology , microbiology and biotechnology , cancer research , genetics
Aurora A kinase plays an essential role in the proper assembly and function of the mitotic spindle. We have shown previously that Aurora A expression is increased aberrantly in human T‐cell leukemia virus type 1 (HTLV‐1)‐infected T‐cell lines and primary adult T‐cell leukemia cells, and a pan‐Aurora kinase inhibitor, which inhibits both Aurora A and Aurora B kinases, reduces viability and induces apoptosis in these cells. However, the specific effects of Aurora A inhibition on HTLV‐1‐infected T‐cells are poorly understood. In this study, we addressed this question by comparing the effects of MLN8237, a selective inhibitor of Aurora A, on cell viability, cell cycle progression, and induction of apoptosis in HTLV‐1‐infected and ‐uninfected T‐cell lines. MLN8237 reduced the viability of HTLV‐1‐infected T‐cell lines within 24 h, but its effects on that of HTLV‐1‐uninfected T‐cell lines were moderate. MLN8237 induced early apoptosis of HTLV‐1‐infected T‐cell lines without induction of polyploidy. It induced p53 and p21 expression in HTLV‐1‐infected but not in ‐uninfected T‐cell lines, suggesting that MLN8237‐treated HTLV‐1‐infected T‐cell lines exit from mitosis and activate a p53‐dependent postmitotic G 1 checkpoint, leading to G 1 arrest followed by the induction of apoptosis. Our results suggest that specific inhibition of Aurora A kinase is a potentially useful therapeutic strategy in the treatment of adult T‐cell leukemia and that further in vivo exploration is warranted. ( Cancer Sci 2010; 101: 1204–1211)