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Benzalkonium Chloride Enhances Cell Death Induced by Etoposide in a p53-independent Manner

Undergraduate #9
Discipline: Biological Sciences
Subcategory: Cell and Molecular Biology
Session: 2
Room: Exhibit Hall

Dianah Anderson - Savannah State University
Co-Author(s): Zarin Bhuiyan, Savannah State University, Savannah, GA; Hua Zhao, University of Minnesota, St. Paul,MN; Takayuki Nitta, Savannah State University, Savannah, GA.



Benzalkonium chloride (BKC) induces various biological effects, and showed cytotoxicity on cells such as conjunctival cells, lymphocytes and nasal mucosa, but mechanisms of cell death induced by BKC, and its potential application in cancer and transformed cells remains elusive. We found that cytotoxic effects of BKC varied among the cancer and transformed cells. In particularly, the combination of BKC and an apoptosis inducer cholinium salt of betulinic acid grafted with glycine ([cholinium][BA-Gly]) showed synergistic inhibitory effects on the growth of 293T cells and induced cell death. Treatment of each [cholinium][BA-Gly], etoposide and high dose of BKC activated molecules involved in apoptosis. but, co-treatment of low dose of BKC attenuated apoptosis signals induced by [cholinium][BA-Gly] and etoposide and increased propidium iodide- and trypan blue-stained cells. Etoposide induces apoptosis through DNA-PK, phosphorylation of p53 and transcription of Bax in a mouse fibroblast cell line L929, but co-treatment of wortmannin or cycloheximide did not rescue cell death induced by etoposide in 293T cells. These data suggested that BKC could shift the death signaling pathways from apoptosis to necroptosis through DNA-PK- and p53-independent pathways and demonstrated that potential application of BKC in cancer and toxicological researches. To clarify the pathways affected by BKC, metabolic activities, expression and modification of proteins in apoptosis and necroptosis have been investigated.

Funder Acknowledgement(s): NSFHBCU-UP

Faculty Advisor: Takuyuki Nitta, nittat@savannahstate.edu

Role: cell culture, cytotoxic assay, and western block.

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This material is based upon work supported by the National Science Foundation (NSF) under Grant No. DUE-1930047. Any opinions, findings, interpretations, conclusions or recommendations expressed in this material are those of its authors and do not represent the views of the AAAS Board of Directors, the Council of AAAS, AAAS’ membership or the National Science Foundation.

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