Molecular effectors and modulators of hypericin-mediated cell death in bladder cancer cells

被引：81

作者：

Buytaert, E. ^{[1
]}

Matroule, J. Y. ^{[2
]}

Durinck, S. ^{[3
]}

Close, P. ^{[2
]}

Kocanova, S. ^{[1
]}

Vandenheede, J. R. ^{[1
]}

de Witte, P. A. ^{[4
]}

Piette, J. ^{[2
]}

Agostinis, P. ^{[1
]}

机构：

[1] Catholic Univ Louvain, Fac Med, Dept Mol & Cell Biol, Brabant, Belgium

[2] Univ Liege, Lab Virol & Immunol, Liege, Belgium

[3] Catholic Univ Louvain, Dept Elect Engn, ESAT SCD, Brabant, Belgium

[4] Catholic Univ Louvain, Fac Pharm, Lab Pharmaceut Biol & Phytopharmacol, Brabant, Belgium

来源：

ONCOGENE | 2008年 / 27卷 / 13期

关键词：

photodynamic therapy; microarrays; p38(MAPK);

D O I：

10.1038/sj.onc.1210825

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Photodynamic therapy (PDT) is an anticancer approach utilizing a light-absorbing molecule and visible light irradiation to generate, in the presence of O-2, cytotoxic reactive oxygen species, which cause tumor ablation. Given that the photosensitizer hypericin is under consideration for PDT treatment of bladder cancer we used oligonucleotide microarrays in the T24 bladder cancer cell line to identify differentially expressed genes with therapeutic potential. This study reveals that the expression of several genes involved in various metabolic processes, stress-induced cell death, autophagy, proliferation, inflammation and carcinogenesis is strongly affected by PDT and pinpoints the coordinated induction of a cluster of genes involved in the unfolded protein response pathway after endoplasmic reticulum stress and in antioxidant response. Analysis of PDT-treated cells after p38(MAPK) inhibition or silencing unraveled that the induction of an important subset of differentially expressed genes regulating growth and invasion, as well as adaptive mechanisms against oxidative stress, is governed by this stress-activated kinase. Moreover, p38(MAPK) inhibition blocked autonomous regrowth and migration of cancer cells escaping PDT-induced cell death. This analysis identifies new molecular effectors of the cancer cell response to PDT opening attractive avenues to improve the therapeutic efficacy of hypericin-based PDT of bladder cancer.

引用

页码：1916 / 1929

页数：14

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