Charge-dependent Targeting: Results in Six Tumor Cell Lines

• Published in: Anticancer research Vol. 24; no. 3A; pp. 1347 - 1351
• Main Authors: MARQUEZ, Marcela, NILSSON, Sten, LENNARTSSON, Lena, ZHAOXU LIU, TAMMELA, Teuvo, RAITANEN, Mika, HOLMBERG, Anders R
• Format: Journal Article
• Language: English
• Published: Attiki International Institute of Anticancer Research 01-05-2004
• Subjects: Biological and medical sciences; Cations; Cell Division - drug effects; Cell Line, Tumor; Dextrans - pharmacology; Dose-Response Relationship, Drug; Female; Humans; Male; Medical sciences; Medicin och hälsovetenskap; Microscopy, Fluorescence; N-Acetylneuraminic Acid - metabolism; Neoplasms - drug therapy; Neoplasms - metabolism; Neoplasms - pathology; Tumors; Dextran; Sialic acid; Cancerology; cationic dextran; Blood substitute; Established cell line; Inhibitor; growth inhibition; Tumor cell
• ISSN: 0250-7005; 1791-7530

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.