Effects of flavonoids on cisplatin-induced apoptosis of HL-60 and L1210 leukemia cells

Received 7 January 2002; accepted 1 April 2002.

Abstract

Effects of three flavonoids, quercetin (QU), galangin (GA), and chrysin (ChR) on cisplatin (cis-Pt)-induced apoptosis of human promyelocytic leukemia HL-60 cells and murine leukemia L1210 cells were investigated. The quantitative analysis of apoptotic DNA fragmentation was used to show that preincubation of cells with flavonoids can influence cis-Pt-induced apoptosis in different way. ChR had no effect, QU enhanced, and GA reduced apoptotic DNA fragmentation. It is also shown that combined treatment with QU and cis-Pt showed synergistic effect, however, GA combined with cis-Pt exhibited antagonism on cytotoxicity in L1210 murine leukemia cells. We assume that tested flavonoids affect the important biological activities connected with cancer chemotherapy and chemoprevention as they differently modulated the sensitivity of cells to cis-Pt treatment. QU is presented as pro-apoptotic agent and GA as agent with anti-apoptotic potential.

Abbreviations: HL-60, human promyelocytic leukemia cell line, L1210, murine leukemia cell line, MTT, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide, QU, quercetin, GA, galangin, ChR, chrysin, PKC, protein kinase C, H2O2, hydrogen peroxide, PARP, poly(ADP-ribose) polymerase

Keywords: Quercetin, Galangin, Chrysin, Cisplatin, Apoptosis, HL-60, L1210

a Cancer Research Institute, Vlárska 7, 833 91 Bratislava, Slovak Republic

b Department of Genetics, Faculty of Sciences, Comenius University, Mlynská dolina, 842 15 Bratislava, Slovak Republic

c Institute of Molecular Biology, Dubravská cesta 21, 842 51 Bratislava, Slovak Republic

d Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kuwait University, P.O. Box 24923 Safat, 13110 Kuwait

Corresponding author. Tel.: +421-2-59327-105; fax: +421-2-59327-250.

PII: S0145-2126(02)00063-2

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