Enzymatically stable unsaturated hyaluronan-derived oligosaccharides with selective cytostatic properties

Area of Science:

• Biochemistry
• Glycosaminoglycan Chemistry
• Extracellular Matrix Biology

Background:

• Hyaluronan (HA), a key extracellular matrix component, influences cellular functions based on its molecular weight and modifications.
• Unsaturated HA oligosaccharides offer therapeutic potential, which can be enhanced through chemical modifications like reduction.
• Previous synthesis of such modified oligosaccharides was not reported.

Purpose of the Study:

• To develop a novel three-step synthesis for unsaturated hyaluronan oligosaccharides with reduced termini.
• To evaluate the enzymatic stability and biological activity of these modified oligosaccharides.
• To investigate their effect on cancer cell growth, independent of CD44 receptor expression.

Main Methods:

• A three-step synthesis involving esterification, depolymerization, and reduction was employed.
• Synthesized oligosaccharides were tested for resistance to mammalian and bacterial hyaluronidases.
• Cell viability assays (MTT and NRU) were performed on human colon carcinoma cells (HT-29) and fibroblasts.

Main Results:

• A novel synthesis yielded unsaturated hyaluronan oligosaccharides with reduced alcohol termini.
• Modified oligosaccharides demonstrated resistance to hyaluronidase degradation.
• These compounds inhibited human colon carcinoma cell growth by 20-50% at 500-1000 μg/mL, irrespective of CD44 expression, without affecting fibroblast growth.

Conclusions:

• Enzymatically stable, modified hyaluronan oligosaccharides were successfully synthesized.
• These novel compounds exhibit anti-proliferative effects on colon cancer cells.
• They represent promising, stable building blocks for developing new biologically active substances.