Growth arrest and apoptosis in adult T cell leukemia cell lines following IL-2 deprivation

• Published in: International journal of oncology Vol. 25; no. 2; p. 437
• Main Authors: Fujimura, Satoshi, Arakawa, Fumiko, Yamada, Yasuaki, Liao, Shaoxi, Khare, Pranay D, Kuroki, Masahide, Ono, Junko
• Format: Journal Article
• Language: English
• Published: Greece 01.08.2004
• Subjects: Adult; Apoptosis; bcl-X Protein; Caspase 3; Caspases - metabolism; Cell Line, Tumor; DNA Fragmentation; Enzyme Activation; G1 Phase - physiology; Humans; Interleukin-2 - physiology; Intracellular Space - chemistry; Intracellular Space - metabolism; Leukemia, T-Cell - metabolism; Leukemia, T-Cell - pathology; Membrane Potentials - physiology; Mitochondria - physiology; Proto-Oncogene Proteins c-bcl-2 - metabolism; Reactive Oxygen Species - analysis; Reactive Oxygen Species - metabolism
• ISSN: 1019-6439
• DOI: 10.3892/ijo.25.2.437

Adult T-cell leukemia (ATL) is a peripheral T-cell neoplasm caused by human T-cell leukemia virus type-I (HTLV-I). Since ATL cells often require IL-2 for their proliferation and survival, we examined the effect of IL-2 deprivation on the IL-2-dependent ATL cells established from ATL patients. After IL-2 withdrawal, these cells were arrested in the G1 phase and then underwent apoptosis. p27Kip1 was observed to act as a cell cycle inhibitor. A decrease in the amount of Bcl-xL was more distinct than that of Bcl-2, while Bax increased slightly during IL-2 withdrawal. The activation of caspase-3 and the loss of mitochondrial membrane potential were also observed. An overexpression of Bcl-xL protein in the KK1, one of the ATL cell lines, suppressed apoptosis by the 3rd day, however, apoptosis could not be prevented completely. Thereafter, a decrease in Bcl-xL and an activation of caspase-3 were observed even under the overexpression of Bcl-xL. The mitochondrial membrane potential and the intra-cellular levels of reactive oxygen species (ROS) also changed due to IL-2 deprivation. From these results, the IL-2 signals are considered to be essential for the survival of ATL cells, and the interruption of IL-2 signaling might thus be useful as a potentially new treatment for ATL.