RT Journal Article SR Electronic T1 Tumor-specificity and Type of Cell Death Induced by Vitamin K2 Derivatives and Prenylalcohols JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 151 OP 158 VO 28 IS 1A A1 HIROSHI SAKAGAMI A1 KEN HASHIMOTO A1 FUMIKA SUZUKI A1 MARIKO ISHIHARA A1 HIROTAKA KIKUCHI A1 TADASHI KATAYAMA A1 KAZUE SATOH YR 2008 UL http://ar.iiarjournals.org/content/28/1A/151.abstract AB Fourteen vitamin K2 (menaquinone (MK)-n, n=1~14) and ten prenylalcohol derivatives (n=1~10) with different numbers (n) of isoprenyl groups in the side chains were investigated for their cytotoxicity against nine human tumor cell lines and three human normal oral cells. Among the vitamin K2 derivatives, MK-2 (n=2) showed the greatest cytotoxicity, followed by MK-1 (n=1) and MK-3 (n=3). MK-1, MK-2 and MK-3 showed the highest tumor-specific index (TS= >2.0, 2.0 and >1.7, respectively). Among the prenylalcohols, geranylgeraniol (GG) (n=4) showed the highest cytotoxicity, followed by farnesol (n=3) and geranylfarnesol (GF) (n=3). GG showed the highest tumor-specificity (TS=1.8), followed by farnesol (TS=>1.4), GF (TS=> <1.3). However, the tumor-specificity of MK-2 and GG was much lower than that of conventional chemotherapeutic agents. The human leukemic cell lines were the most sensitive, whereas the human glioblastoma cell lines were the most resistant to MK-2 and GG. MK-2 did not induce internucleosomal DNA fragmentation in either the human promyelocytic leukemia HL-60 or the human squamous cell carcinoma HSC-4 cell lines. GG induced marginal internucleosomal DNA fragmentation in the HL-60 cells, but not in the HSC-4 cells. Both MK-2 and GG did not induce the formation of autophagosomes, nor did they clearly change the intracellular concentration of three polyamines. Electron spin resonance (ESR) spectroscopy showed that only MK-1 (n=1), as well as GGF (n=7) and GFF (n=8) which had lower cytotoxicity, produced radicals, suggesting the lack of connection between cytotoxicity and radical production. The present study demonstrates that the presence of 1,4-naphtoquinone structure (including α,β-unsaturated ketones) in vitamin K2 derivatives confers on them the ability to induce non-apoptotic cell death.