Saccharin and cyclamate inhibit binding of epidermal growth factor

Area of Science:

• Cell Biology
• Biochemistry
• Toxicology

Background:

• Epidermal Growth Factor (EGF) is crucial for cell growth and differentiation.
• Tumor promoters like phorbol esters are known to interfere with EGF signaling.
• The effect of artificial sweeteners on EGF binding was previously unexplored.

Purpose of the Study:

• To investigate the impact of saccharin and cyclamate on EGF binding to various cell lines.
• To compare the sensitivity of human, rodent, and canine cells to sweetener-induced inhibition of EGF binding.
• To explore potential mechanisms underlying EGF binding inhibition by diverse compounds.

Main Methods:

• Radioligand binding assay using 125I-labeled mouse EGF.
• Testing inhibition by saccharin and cyclamate across 18 different cell lines (human, rodent, canine).
• Dose-response studies and reversal experiments with excess EGF.

Main Results:

• Saccharin and cyclamate significantly inhibited EGF binding in all tested cell lines.
• Human cell lines (HeLa, HF, GM17, XP) showed higher sensitivity to inhibition compared to rodent (HTC, K22, 3T3-L1) and canine (MDCK) cells.
• While high EGF doses reversed inhibition in rodent cells, they were ineffective in HeLa cells.
• Other sugars (glucose, sucrose) and sugar alcohols (xylitol, 2-deoxyglucose) did not affect EGF binding.

Conclusions:

• Saccharin and cyclamate interfere with EGF receptor binding, with differential sensitivity across species.
• The findings suggest a potential common pathway for EGF binding inhibition by unrelated molecules like sweeteners and phorbol esters.
• Activation of a hormone response control unit is proposed as a unifying mechanism for this inhibition.