Aloe-emodin Induces Cell Death through S-Phase Arrest and Caspase-dependent Pathways in Human Tongue Squamous Cancer SCC-4 Cells

作者:Chiu Tsan Hung; Lai Wan Wen; Hsia Te Chun; Yang Jai Sing; Lai Tung Yuan; Wu Ping Ping; Ma Chia Yu; Yeh Chin Chung; Ho Chin Chin; Lu Hsu Feng; Wood W Gibson; Chung Jing Gung*
来源:Anticancer Research, 2009, 29(11): 4503-4511.

摘要

Aloe-emodin, one of the anthraquinones, has been shown to have anticancer activity in different kinds of human cancer cell lines. Therefore, the purpose of this stud), was to investigate the anti-cancer effect of aloe-emodin on human tongue squamous carcinoma SCC-4 cells. The results indicated that aloe-emodin induced cell death through S-phase arrest and apoptosis in a dose- and time-dependent manner. Treatment with 30 mu M of aloe-emodin led to S-phase arrest through promoted p53, p21 and p27, but inhibited cyclin A, E, thymidylate synthase and Cdc25A levels. Aloe-emodin promoted the release of apoptosis-inducing factor (AIF), endonuclease G (Endo G), pro-caspase-9 and cytochrome c from the mitochondria via a loss of the mitochondrial membrane potential (Delta Psi(m)) which was associated with a increase in the ratio of B-cell lymphoma 2-associated X protein (Bax)/B cell lymphoma/leukemia-2 (Bcl-2) and activation of caspase-9 and -3. The free radical scavenger N-acetylcysteine (NAC) and caspase inhibitors markedly blocked aloe-emodin-induced apoptosis. Aloe-emodin thus induced apoptosis in the SCC-4 cells through the Fas/death-receptor, mitochondria and caspase cascade. Aloe-emodin could be a novel chemotherapeutic drug candidate for the treatment of human tongue squamous cancer in the future.