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Tumor-specificity and type of cell death induced by phenoxazines

F. Suzuki ; K. Hashimoto ; M. Ishihara ; Gunnar Westman (Institutionen för kemi- och bioteknik, Organisk kemi) ; Kristin Samuelsson ; M. Kawase ; N. Motohashi ; H. Sakagami
Anticancer Research (0250-7005). Vol. 27 (2007), 6B, p. 4233-4238.
[Artikel, refereegranskad vetenskaplig]

Phenoxazines have shown diverse biological activities, but tumor-specific cytotoxic activity has not been investigated. A total of 24 phenoxazine derivatives (WM1-24) was investigated for their relative cytotoxicity against human tumor cell lines vs. normal cells. WM7 and WM8 showed the highest tumor-specificity index of 4.3 and 4.8, respectively. Considerable difference in drug-sensitivity was found among these tumor cell lines. Human promyelocytic leukemia HL-60 cells showed the highest sensitivity to both WM7 and WM8, followed by human oral squamous cell carcinoma (HSC-2, HSC-3, HSC-4), and human gingival fibroblast (HGF), pulp cell (HPC) and periodontal ligament fibroblast (HPLF) were the most resistant. WM7 and WM8 induced little or no internucleosomal DNA fragmentation, and activated caspase-3 in HSC-2, HSC-4 and human glioblastoma T98G cells. These compounds failed to induce autophagic cell death, as judged by acridine orange and microtubule-associated protein I light chain 3 (LC3)-GFP assays. These results suggested that the higher cytotoxicity of WM7 and WM8 are derived from the positively-charged quaternary nitrogen substituents on the phenoxazine ring and the electron density of nitrogen at N12, and that inhibition of autophagy is not always coupled with apoplosis induction.

Nyckelord: phenoxazines, cytotoxicity, cell death, caspase, type of cell death, INDUCED APOPTOSIS, INHIBITORS, KETONES, POTENT, LINES



Denna post skapades 2008-12-10. Senast ändrad 2016-02-01.
CPL Pubid: 80898

 

Institutioner (Chalmers)

Institutionen för kemi- och bioteknik, Organisk kemi (2006-2014)
Institutionen för kemi (2001-2011)

Ämnesområden

Kemiteknik

Chalmers infrastruktur