Cancer cell selective probe by mimicking EGCG

Area of Science:

• Biochemistry
• Molecular Biology
• Oncology

Background:

• Proteins overexpressed in cancer cells are key targets for molecular imaging and drug delivery.
• The 67-kDa laminin receptor (67LR), or oncofetal antigen, is overexpressed in various cancers (melanoma, multiple myeloma, cervical, bile duct) and promotes tumor growth, metastasis, and drug resistance.
• Green tea polyphenol (-)-epigallocatechin-3-O-gallate (EGCG) binds to cell-surface 67LR, inducing apoptosis via the Akt/eNOS/NO/cGMP pathway.

Purpose of the Study:

• To identify the optimal hydroxyl group for utilizing EGCG as a fluorescent imaging probe.
• To develop a novel 67LR-targeting fluorescent probe based on EGCG's agonist properties.
• To evaluate the probe's efficacy in cancer cell imaging and therapeutic targeting.

Main Methods:

• Synthesis of EGCG-mimic fluorescent probes with optimized hydroxyl groups.
• Assessment of probe binding specificity using non-labeled EGCG competitive assays.
• Confirmation of 67LR-specific targeting via 67LR knockdown experiments.
• Evaluation of probe-induced Akt activation and inhibition of viable cancer cell number.

Main Results:

• The study identified an optimum hydroxyl group for creating a fluorescent EGCG-mimic probe.
• The developed probe demonstrated specific binding to 67LR on cancer cells.
• Competitive assays and knockdown studies confirmed the probe's 67LR specificity.
• The probe effectively targeted multiple myeloma cells with higher affinity compared to normal cells.

Conclusions:

• A novel fluorescent probe mimicking EGCG has been developed for 67LR-targeted molecular imaging.
• This probe exhibits specific binding to 67LR and potential for cancer imaging and therapy.
• The probe shows preferential binding to multiple myeloma cells, suggesting diagnostic and therapeutic applications.