Aloe-emodin induces cell death through S-phase arrest and caspase-dependent pathways in human tongue squamous cancer SCC-4 cells.
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 study 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 microM 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 (DeltaPsi(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.
Chiu
Tsan-Hung
TH
Department of Biological Science and Technology, China Medical University, Taiwan, Republic of China.
Lai
Wan-Wen
WW
Hsia
Te-Chun
TC
Yang
Jai-Sing
JS
Lai
Tung-Yuan
TY
Wu
Ping-Ping
PP
Ma
Chia-Yu
CY
Yeh
Chin-Chung
CC
Ho
Chin-Chin
CC
Lu
Hsu-Feng
HF
Wood
W Gibson
WG
Chung
Jing-Gung
JG
D000880:Anthraquinones / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D004706:Endodeoxyribonucleases / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D017382:Reactive Oxygen Species / Q000378:metabolism; D016196:S Phase / Q000187:drug effects*; D014062:Tongue Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D000880:Anthraquinones; D000970:Antineoplastic Agents; D007527:Isoenzymes; D017382:Reactive Oxygen Species; C518327:aloe emodin; D004706:Endodeoxyribonucleases; C052391:endonuclease G; D020169:Caspases; D002118:Calcium