CCN5 activation by free or encapsulated EGCG is required to render triple‐negative breast cancer cell viability and tumor progression

Pharmacology Research & Perspectives

Inamul Haque¹  Arnab Ghosh¹  Indranil Chatterjee¹  Amlan Das¹  Sushanta K. Banerjee¹  Snigdha Banerjee¹  Archana De¹  Priyanka Ray²  Debasmita Dutta³  Mohiuddin Quadir³  Sumedha Gunewardena⁴  Scott Weir⁵ 

[1] Cancer Research Unit VA Medical Center Kansas City MO USA;Department of Chemical Biochemical Environmental Engineering (CBEE University of Maryland Baltimore MD USA;Department of Coatings and Polymeric Materials North Dakota State University Fargo ND USA;Department of Molecular and Integrative Physiology University of Kansas Medical Center Kansas City KS USA;Department of Pharmacology Toxicology and Therapeutics University of Kansas Medical Center Kansas City KS USA;

关键词: bioavailability;    breast cancer;    CCN5;    drug delivery;    EGCG;    FA‐PEG‐NPs;   

DOI  :  10.1002/prp2.753

来源: DOAJ

【 摘 要 】

Abstract 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 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. We demonstrate that EGCG activates CCN5 to inhibit in vitro cell viability through apoptosis, the sphere‐forming ability via reversing TNBC cells’ stemness, 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. Together, these studies identify EGCG (free or encapsulated) as a novel activator of CCN5 in TNBC cells and hold promise as a future therapeutic option for TNBC with upregulated CCN5 expression.

【 授权许可】

Unknown