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Induction of Apoptosis by Ionizing Radiation and CI-1033 in HuCCT-1 Cells

Induction of Apoptosis by Ionizing Radiation and CI-1033 in HuCCT-1 Cells

Masateru Murakami, Tamito Sasaki, Souichirou Yamasaki, Kenichi Kuwahara, Hideki Miyata, Kazuaki Chayama

Biochem Biophys Res Commun. 2004 Jun 18;319(1):114-9.

PMID: 15158449

Abstract:

CI-1033 is a quinazoline-based HER family tyrosine kinase inhibitor that is currently being evaluated as a potential anticancer agent. The present study examines the molecular mechanism by which CI-1033 induces apoptosis either as a single agent or in combination with radiation. Although CI-1033 alone did not induce apoptosis, the simultaneous exposure of cells to CI-1033 and radiation induced significant levels of apoptosis. The sequential treatment of cells with CI-1033 followed by radiation induced an even greater effect with 62.6% of cells undergoing apoptosis but this enhanced effect was not seen if cells were treated first with radiation and then CI-1033. The combination treatment induces apoptosis of HuCCT-1 via upregulation of FasL and Bid cleavage. These data suggest that modulation of the Fas-FasL pathway and activation of Bid could be useful for increasing the anti-tumor effect of CI-1033 in this type of cancer.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP289499452	CI-1033		289499-45-2	Price

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