MET-Mediated Drug Resistance in Colorectal Cancer: In Silico Analysis of the Potential of Epicatechin-3-Gallate and Epigallocatechin-3-Gallate as Therapeutic Adjuvants

Abstract

Background: Colorectal cancer (CRC) is the third most common cancer worldwide by incidence and the second leading cause of cancer-related death. Although chemotherapy has improved survival rates, long-term use often leads to chemoresistance and significant side effects. Therefore, new adjuvant strategies are urgently needed. This study examines the potential of tea catechins (Camellia sinensis), specifically epigallocatechin-3-gallate (EGCG) and epicatechin-3-gallate (ECG), as adjuvants to overcome chemoresistance in CRC.
Methods: We used a computational approach combining network pharmacology and molecular docking.
Results: Protein target analysis showed that ECG and EGCG specifically target four proteins, including the key hub protein c-Met (MET). The MET protein plays a vital role in CRC chemoresistance, especially in response to anti-angiogenic therapy. This potential is supported by patient survival data indicating a poor prognosis for CRC patients with MET overexpression. The molecular docking results suggest that EGCG and ECG bind strongly to c-Met, with binding energies of -9.2 kcal/mol and -9.1 kcal/mol, respectively. This high affinity supports the idea that ECG and EGCG can directly modulate c-Met's various functions.
Conclusion: This in silico study provides a solid molecular basis for developing tea catechins as chemosensitizers to improve chemotherapy effectiveness and reduce chemoresistance in CRC.