PT  - JOURNAL ARTICLE
AU  - MARCELA MARQUEZ
AU  - STEN NILSSON
AU  - LENA LENNARTSSON
AU  - ZHAOXU LIU
AU  - TEUVO TAMMELA
AU  - MIKA RAITANEN
AU  - ANDERS R. HOLMBERG
TI  - Charge-dependent Targeting: Results in Six Tumor Cell Lines
DP  - 2004 May 01
TA  - Anticancer Research
PG  - 1347--1352
VI  - 24
IP  - 3A
4099  - http://ar.iiarjournals.org/content/24/3A/1347.short
4100  - http://ar.iiarjournals.org/content/24/3A/1347.full
SO  - Anticancer Res2004 May 01; 24
AB  - Background: Many previous studies show that cell surface sialylation of malignant cells is enhanced compared to normal tissue. The carboxyl group of the sialic acid yields a negative surface charge of the tumor cells. This study investigates how tumor cell growth is affected when a cationic polymer is incubated with six different tumor cell lines. Materials and Methods: Cationic dextran (CatDex) was prepared by periodate oxidation and subsequent coupling of cationic sidegroups by reductive amination. A fluorimetric cytotoxicity assay (FMCA) was used for the cell survival assay. Six different tumor cell lines (lung, breast, ovarian, prostate, colon, urinary bladder) were seeded into 96-well microtiter plates. CatDex was added at different μM concentrations and incubated for 72 h. Additionally, CatDex was fluorescence-labeled (FITC) and the interaction with the tumor cells was studied using fluorescence microscopy. The presence of sialic acid in the different cell lines was confirmed by using a FITC-labeled sialic acid binding lectin. Results: CatDex showed a concentration-dependent growth inhibitory effect (i.e. the number of cationic side groups/ dextran molecule and the molarity used). If the substitution was <20%, the growth inhibitory effect was small and difficult to reproduce. With 20-22% substitution, the growth inhibition varied between 20-95% depending on the molarity and the tumor type. Higher substitution resulted in complete cell death in all the cell lines. The fluorescent images showed intensive cell membrane interaction. Conclusion: Incubation with cationic dextran caused cell death in all six tumor cell lines. Our hypothesis is that CatDex binds to the anionic sialic acid residues and causes fatal disturbances in the cell membrane. However the exact mechanism remains to be elucidated. The results may indicate a new method of general interest for intra/local/regiolocal treatment of cancer. Clinical studies to explore this concept are pending. Copyright© 2004 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved