[Effect of caffeine on camptothecin-induced apoptosis of Molt-4 cells].
OBJECTIVE
Caffeine could act on cell cycle checkpoints and affect the progression of cell cycle, but its impact on apoptosis of tumor cells is in debate. This study was carried out to investigate the effects of caffeine on camptothecin-induced apoptosis and cell cycle checkpoints of leukemia cell line Molt-4.


METHODS
The cell apoptosis was induced by camptothecin, and caffeine was used to interfere with cell cycle checkpoints. The apoptosis rate and cell cycle during apoptosis were analyzed using sub-G1 method and Annexin V-propidium iodide (Annexin V/PI) staining.


RESULTS
Caffeine (2.0-20.0 mmon/L) had no effect on proliferation of Molt-4 cells in exponentially growth phase. Camptothecin selectively induced apoptosis of Molt-4 cells in S phase; when induced with camptothecin (0.15 micromol/L) for 4 or 6 h, the apoptosis rates were (23.69+/-2.26)% and (36.99+/-1.42)%. This cell cycle-specific apoptosis were inhibited obviously by caffeine with the apoptosis rates of (4.79+/-0.64)% and (2.69+/-0.56)%. When caffeine was removed, the apoptosis rates increased obviously to (46.23+/-0.21)% and (55.81+/-0.41)%, and still mainly happened in S phase.


CONCLUSIONS
Caffeine could inhibit camptothecin-induced apoptosis of Molt-4 cells. As a drug acting on cell cycle checkpoints, caffeine could transiently shield the surveillance of checkpoints to damaged cells and inhibit cell apoptosis. The effect may be reversed when caffeine is removed away.
Tan
Hui-Ling
HL
Molecular Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P. R. China.
Feng
Yong-Dong
YD
Tao
De-Ding
DD
Xiao
Hui
H
Xie
Da-Xing
DX
Yu
Cong-Nian
CN
Gong
Jian-Ping
JP
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002110:Caffeine / Q000494:pharmacology*; D002166:Camptothecin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D015458:Leukemia, T-Cell / Q000473:pathology*; D016196:S Phase
D000972:Antineoplastic Agents, Phytogenic; D002110:Caffeine; D002166:Camptothecin