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. 2003 Jan 28;32(1):63–73. doi: 10.1046/j.1365-2184.1999.3210063.x

Induction of apoptosis by hinokitiol, a potent iron chelator, in teratocarcinoma F9 cells is mediated through the activation of caspase‐3

Y Ido 1, N Muto 2, A Inada 3, J Kohroki 1, M Mano 1, T Odani 1, N Itoh 1, K Yamamoto 4, K Tanaka 1
PMCID: PMC6726316  PMID: 10371304

Abstract

Abstract. Hinokitiol, a potent iron chelator, has been reported to induce differentiation in teratocarcinoma F9 cells with a reduction of viable cells. In this study, we examined the steps leading to eventual cell death by hinokitiol during differentiation. Hinokitiol induced DNA fragmentation of F9 cells in a concentration‐and time‐dependent manner. This effect was also observed in a cell‐free system using the nuclei from intact cells and the cytosols from hinokitiol‐treated cells. In contrast, hinokitiol methyl ether and hinokitiol‐‐Fe (III) complex, which are deficient in iron‐chelating activity, showed no DNA fragmentation activity in both cell culture and cell‐free systems. These results suggest that iron deprivation by hinokitiol may be involved in the induction of apoptosis of F9 cells. Caspase‐3, one of the key enzymes in the apoptotic cascade, was specifically activated by hinokitiol treatment, but not by the other two derivatives. In addition, its specific inhibitor, benzyloxycarbonyl‐Val‐Ala‐Asp‐fluoromethyl ketone, strongly blocked hinokitiol‐induced DNA fragmentation. These results indicate that iron deprivation by hinokitiol can induce apoptosis of F9 cells through the activation of caspase‐3.

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