Growth inhibition of MCF-7 tumor cell line by phenylacetate linked to functionalized dextran.
We investigated the antiproliferative effect of phenylacetate covalently linked to dextran derivatives (DMCBPA conjugates) on human breast cancer MCF-7 cells. We show that free sodium phenylacetate (NaPA) inhibits the cell growth (IC50 = 14 mM), while an important inhibitory effect is observed for DMCBPA conjugates. The IC50 dose of these conjugates is as low as 1.0 mg/ml, corresponding to 1.3 mM of phenylacetate. The precursors, dextran substituted with methylcarboxylate and benzylamide groups, did not affect the growth of MCF-7 tumor cells. We have observed that MCF-7 cell growth inhibition depends on amount of phenylacetate linked to the conjugate. The data indicated that an optimum antiproliferative effect is more significant when the amount of phenylacetate groups present on the dextran backbone is high. Analysis of doubling time by growth kinetics study shows that conjugates have more time-sustained effect than free NaPA. It is noteworthy that the inhibitory effect is observed at non-toxic concentration. Theses conjugates could be considered as acceptable derivatives to prevent tumor progression.
Frank
L
L
Laboratoire de Chimie et Biologie des Biomatériaux, Institut Galilée, Université Paris 13, 99 Avenue Jean-Baptiste Clément, 93430 Villetaneuse, France.
Avramoglou
T
T
Sainte-Catherine
O
O
Jozefonvicz
J
J
Kraemer
M
M
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003911:Dextrans / Q000737:chemistry*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008956:Models, Chemical; D010648:Phenylacetates / Q000737:chemistry* / Q000494:pharmacology
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D003911:Dextrans; D010648:Phenylacetates; C025136:phenylacetic acid