Tumor-specificity and type of cell death induced by phenoxazines
Journal article, 2007

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.

KETONES

INDUCED APOPTOSIS

LINES

cell death

type of cell death

POTENT

cytotoxicity

caspase

phenoxazines

INHIBITORS

Author

F. Suzuki

K. Hashimoto

M. Ishihara

Gunnar Westman

Chalmers, Chemical and Biological Engineering, Organic Chemistry

Kristin Samuelsson

University of Gothenburg

M. Kawase

N. Motohashi

H. Sakagami

Anticancer Research

0250-7005 (ISSN)

Vol. 27 6B 4233-4238

Subject Categories

Chemical Engineering

PubMed

18225595

More information

Created

10/7/2017