Grape seed procyanidin extract against lung cancer: the role of microrna-106b, bioavailability, and bioactivity.

Grape seed procyanidin extract against lung cancer: the role of microrna-106b, bioavailability, and bioactivity. Oncotarget. 2018 Mar 20;9(21):15579-15590 Authors: Xue B, Lu QY, Massie L, Qualls C, Mao JT Abstract MiR-106b is an oncomir and a potential target for anti-cancer therapy. We hypothesize that grape seed procyanidin extract (GSE) exerts antineoplastic effects on lung cancer through modulations of miR-106b and its downstream target. We found that GSE significantly down-regulated miR-106b in a variety of lung neoplastic cells and increased cyclin-dependent kinase inhibitor 1A (CDKN1A) mRNA and protein (p21) levels. Transfection of miR-106b mimics reversed the up-regulations of CDKN1A mRNA and p21, abrogated the GSE induced anti-proliferative and anti-invasive properties in lung cancer cells. Oral gavage of leucoselect phytosome (LP), a standardized GSE to athymic nude mice down-regulated MIR106B mRNA and miR-106b expressions, and increased CDKN1A mRNA expression in tumor xenografts, correlating to significant reduction of tumor growth. To assess bioavailability, GSE and metabolites in plasma levels, between 60-90 minutes after gavage of LP were measured by LC/MS at treatment week 4 and 8. A novel bioactivity assay was also developed using lung homogenates from treated mice co-cultured with human lung cancer cells. LP-treated mouse lung homogenates significantly reduced proliferations of various lung cancer cells. Our findings...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research