Published in Cancer Detection and Prevention 1998; 22(Supplement 1).

MRN-100 depletes glutathione level and increases human head & neck carcinoma Calu-27 sensitivity to natural killer cell cytotoxicity

M Ghoneum PhD, M Al-Bassam PhD

Drew Univ. Med. & Sci. Dept. Otolaryngol. LA, CA 90059, USA

AIM: To examine the in vitro impact of MRN-100 on glutathione (GSH) levels in Calu-27 cells. GSH functions in the maintenance of redox status, conjugation and detoxification of xenobiotics; scavenging reactive oxygen species, and amino acid transport. GSH and glutathione-S-transferase appear to be critical determinants in tumor resistance to several antineoplastic drugs. MRN-100 is an iron based compound derived from bivalent and tervalent ferrates. METHODS: Calu-27 cells were cultured with MRN-100 for 3 d at concentrations of 0-30% v/v. GSH was measured in cell supernatant by a modified Tietze method. RESULTS: 1) MRN-100 significantly depletes GSH level. The effect was dose dependent; 3.1 and 31.2% at concentrations 5 and 10%, respectively. GSH depletion plateaued (25%) at subsequent MRN-100 concentrations of 20 and 30%; 2) treated Calu-27 cells became sensitive to NK cytotoxicity as shown by 51Cr-release assay at E:T ratio 100:1. NK activity was 51.3% for treated Calu-27 as compared to control, 20.4%, > 2 fold increase. CONCLUSION: MRN-100 depletes GSH level and increases sensitivity of Calu-27 to NK cytotoxicity. This may have therapeutic value.

KEY WORDS: head and neck cancer, .

Paper presented at the International Symposium on the Impact of Biotechnology on Prediction, Prevention and Treatment of Cancer; Nice, France; October 24 - 27, 1998; in the section on Immunotherapy.