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

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 reveal novel antineoplastic mechanisms by GSE, further define the pharmacokinetics and pharmacodynamics of LP, and support the continued investigation of LP against lung cancer.

Health Effects of Grape Seed and Skin Extracts and Their Influence on Biochemical Markers

“…To assess bioavailability, GSE and metabolites in plasma levels were measured at weeks 4 and 8 of treatment 60–90 min after the LP probe. The findings show new antineoplastic mechanisms of GSE, further define the pharmacokinetics and pharmacodynamics of LP, and support further research on the use of LP against lung cancer [ 52 ].…”

“…A study conducted by Xue et al [ 52 ] tested the effect of grape procyanidin extract against lung cancer, and its bioavailability and bioactivity. MiR-106b is a potential target for antitumor therapy.…”

Exploring the Antioxidant Effects and Periodic Regulation of Cancer Cells by Polyphenols Produced by the Fermentation of Grape Skin by Lactobacillus plantarum KFY02

“…Resveratrol is a polyhydric phenolic compound. In addition to preventing cardiovascular and cerebrovascular diseases, it also has strong anticancer abilities [28]. Some clinical data have shown that procyanidin oligomers from grape seeds are 20 times more potent than vitamin C and 50 times more potent than vitamin E in antioxidants [29].…”

The effects of grape seed extract (Vitis vinifera) supplement on inflammatory markers, neuropeptide Y, anthropometric measures, and appetite in obese or overweight individuals: A randomized clinical trial

“…Previous reports demonstrated that polyphenolic and gallic acid contents of GSE have a role in scavenging free radicals which possess varieties of valuable health effects (Abhijit et al, ; Frankel, German, Kinsella, Parks, & Kanner, ; Jorge, Ricardo Da Silva, Fernandez, & Mitjavila, ; Safaei et al, ; Shi et al, ; Xue, Lu, Massie, Qualls, & Mao, ). It seems that obesity‐related inflammation is also associated with higher level of oxidative stress (Fernández‐Sánchez et al, ).…”