Substituted titanocenes induce caspase-dependent apoptosis in human epidermoid carcinoma cells in vitro and exhibit antitumour activity in vivo

被引：0

作者：

J H Bannon

I Fichtner

A O'Neill

C Pampillón

N J Sweeney

K Strohfeldt

R W Watson

M Tacke

M M Mc Gee

机构：

[1] UCD School of Biomolecular and Biomedical Science,

[2] Conway Institute of Biomolecular and Biomedical Research,undefined

[3] University College Dublin,undefined

[4] Belfield,undefined

[5] Max Delbrück Center (MDC) for Molecular Medicine,undefined

[6] Robert-Rössle-Straße 10,undefined

[7] UCD School of Medicine and Medical Science,undefined

[8] Conway Institute of Biomolecular and Biomedical Research,undefined

[9] University College Dublin,undefined

[10] Belfield,undefined

[11] UCD School of Chemistry and Chemical Biology,undefined

[12] Centre for Synthesis and Chemical Biology (CSCB),undefined

[13] Conway Institute of Biomolecular and Biomedical Research,undefined

[14] University College Dublin,undefined

[15] Belfield,undefined

来源：

British Journal of Cancer | 2007年 / 97卷

关键词：

titanocene; epidermoid cancer; apoptosis; caspases; chemotherapy; cisplatin;

D O I：

暂无

中图分类号：

学科分类号：

摘要：

Titanocene compounds are a novel series of agents that exhibit cytotoxic effects in a variety of human cancer cells in vitro and in vivo. In this study, the antiproliferative activity of two titanocenes (Titanocenes X and Y) was evaluated in human epidermoid cancer cells in vitro. Titanocenes X and Y induce apoptotic cell death in epidermoid cancer cells, with IC50 values that are comparable to cisplatin. Characterisation of the cell death pathway induced by titanocene compounds in A431 cells revealed that apoptosis is preceded by cell cycle arrest and the inhibition of cell proliferation. The induction of apoptosis is dependent on the activation of caspase-3 and -7 but not caspase-8. Furthermore, the antitumour activity of Titanocene Y was tested in an A431 xenograft model of epidermoid cancer. Results indicate that Titanocene Y significantly reduced the growth of A431 xenografts with an antitumour effect similar to cisplatin. These results suggest that titanocenes represent a novel series of promising antitumour agents.

引用

页码：1234 / 1241

页数：7

共 149 条

[1] Beckhove P(2007)Antitumor activity of Titanocene Y in freshly explanted human breast tumours and in xenografted Mcf-7 tumors in mice Anticancer Drugs 18 311-315
[2] Hanauske A-R(2002)Cisplatin-induced renal cell apoptosis: caspase 3-dependent and -independent pathways J Pharmacol Exp Ther 302 8-17
[3] Oberschmidt O(2004)Cytotoxicity, DNA strand breakage and DNA-protein crosslinking by a novel transplatinum compound in human A2780 ovarian and MCF-7 breast carcinoma cells Biochem Pharmacol 68 857-866
[4] Pampillon C(1999)Chemistry and biology of multifunctional DNA binding agents Top Biol Inorg Chem 1 99-115
[5] Schirrmacher V(2006)Anti-tumor activity of Titanocene Y in xenografted Caki-1 tumors in mice Anticancer Drugs 17 333-336
[6] Strohfeldt K(1999)Anticancer activity of cisplatin and related complexes Top Biol Inorg Chem 1 1-43
[7] Sweeney NJ(2001)Is cisplatin-induced cell death always produced by apoptosis? Mol Pharmacol 59 657-663
[8] Tacke M(2001)Reduction of substituted fulvenes studied by spectro-electrochemistry and ab initio theory J Mol Struct 559 331-339
[9] Cummings BS(1999)Structure, recognition, and processing of cisplatin–DNA adducts Chem Rev 99 2467-2498
[10] Schnellmann RG(2003)Why target apoptosis in cancer treatment? Mol Cancer Ther 2 573-580

← 1 2 3 4 5 6 7 8 9 10 →