Aloe-emodin induces cell death through S-phase arrest and caspase-dependent pathways in human tongue squamous cancer SCC-4 cells

Tsan Hung Chiu, Wan Wen Lai, Te Chun Hsia, Jai Sing Yang, Tung Yuan Lai, Ping Ping Wu, Chia Yu Ma, Chin Chung Yeh, Chin Chin Ho, Hsu Feng Lu, W. Gibson Wood, Jing Gung Chung

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74 Scopus citations

Abstract

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 μM 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 (ΔΨm) 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.

Original languageEnglish (US)
Pages (from-to)4503-4511
Number of pages9
JournalAnticancer Research
Volume29
Issue number11
StatePublished - Nov 2009

Keywords

  • Aloe-emodin
  • Apoptosis
  • Caspase
  • Human tongue cancer SCC-4 cells

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