Caspase 14 is a green tea polyphenol-targeted gene that expresses during terminal differentiation of certain epithelial cells such as epidermal keratinocytes. The expression of caspase 14 is involved in cornification and barrier formation of the skin characterized by an undefined cell death mechanism, referred to as planned cell death. In contrast, skin cancer cells lost the ability to produce caspase 14. OBJECTIVES: to develop constructs containing full length cDNA of human caspase 14 or green fluorescent protein (GFP) and transfect human oral cancer (OSC2) and skin cancer (A431) cells with these vectors, and determine if the expression of caspase 14 induce cell death in these tumor cells or reduce the tumorigenicity in athymic mice. METHODS: an oral cancer cell line OSC2, a salivary gland cancer cell line HSG, and a skin cancer cell line A431 were transfected with caspase 14 cDNA and co-transfected with GFP, negative controls were OSC2, HSG and A431 cells transfected with GFP only. Cells were monitored by microscopic photography, the intensity of green fluorescence, and cell viability (MTT) and caspase 3 activity assays. The transfected A431 cells were xenografted into athymic mice to determine the tumorigenicity. RESULTS: expression of caspase 14 induced rapid cell deaths in OSC2, HSG and A431 cells compared to the GFP-expressing controls. Only one subclone of caspase 14-expressing A431 was able to be subcultured, and this subclone demonstrated reduced tumorigenicity in athymic mice. CONCLUSION: OSC2, HSG and A431 cells undergo cell death without caspase 3 activity when caspase 14 expression was restored in these undifferentiated tumor cells. Caspase 14 expression in A431 skin cancer cells reduced tumorigenicity in vivo. Thus, caspase 14 could be used as a potential therapeutic tool to treat certain epithelial cancers, pending further investigation. This study was supported in part by a NIH grant R21 CA097258 to S.H.

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