期刊
ARCHIV DER PHARMAZIE
卷 351, 期 12, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/ardp.201800128
关键词
anticancer agent; cytotoxicity; oxidative stress; pyridazin-(2H)-3-ones; triple-negative breast cancer
资金
- Lalla Salma Foundation: Prevention and Treatment of Cancer [09/AP 2013]
Triple-negative breast cancer (TNBC) is a complex and aggressive subtype of breast cancer characterized by high morbidity and mortality. In the absence of targeted therapy, only chemotherapy is available in this case of cancer. The current study investigated the antitumor effect of new pyridazin-3(2H)-one derivatives on the human TNBC cell line, MD-MB-468. The in vitro cytotoxic activities were investigated using the tetrazolium-based MTT assay. Lipid peroxidation, H2O2 content, and the specific activities of antioxidant enzymes were also determined. Two molecules, 6f and 7h, were found to be selectively highly active against tumor cells with IC50 values of 3.12 and 4.9 mu M, respectively. Furthermore, cells exposed to 6f showed a significant increase in H2O2 and lipid peroxidation levels, accompanied by a decrease in the enzyme activities of glutathione reductase (GR) and thioredoxin reductase (TrxR). The cytotoxicity of the compound 6f may improve the therapeutic efficacy of the current treatment for TNBC via the inhibition of GR and TrxR activities.
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