| Popis: |
Background and Purpose: Epigallocatechin-3-gallate (EGCG) has been considered an anticancer agent despite conflicting and discrepant bioavailability views. EGCG impairs the viability and self-renewal capacity of triple-negative breast cancer (TNBC) cells and makes them sensitive to estrogen via activating ER-α. Surprisingly, the mechanism of EGCG’s action on TNBC cells remains unclear. CCN5/WISP-2 is a gatekeeper gene that regulates viability, ER-α, and stemness in triple-negative breast cancer (TNBC) and other types of cancers. This study aimed to investigate whether EGCG (free or encapsulated in nanoparticles) interacts with the CCN5 protein by emphasizing its bioavailability and enhancing its anticancer effect. Experimental Approach: Nanoparticle preparation, immunohistochemistry, confocal microscopy, Western blotting, qRT-PCR, cell viability assay, apoptosis, and mammosphere techniques were used to investigate the role of CCN5 in EGCG mediated suppression of TNBC cells’ viability, and self-renewal capacity was investigated using appropriate in vitro and in vivo models. Key Results: We demonstrate that EGCG activates CCN5 to inhibit in vitro cell viability through apoptosis, the sphere-forming ability via reversing stemness of TNBC cells, and suppressing tumor growth in vivo. Moreover, we found EGCG-loaded nanoparticles to be functionally more active and superior in their tumor-suppressing ability than free-EGCG. Conclusion and Implications: Together, these studies identify EGCG as a novel activator of CCN5 in TNBC cells and beyond and a key player in anticancer therapy. Moreover, nanoparticle-mediated delivery of EGCG is a potentially attractive and effective therapeutic option for treating TNBC patients and other aggressive cancers. |
