MicroRNA-19a/b mediates grape seed procyanidin extract-induced anti-neoplastic effects against lung cancer

Abstract

Oncomirs are microRNAs (miRNA) associated with carcinogenesis and malignant transformation. They have emerged as potential molecular targets for anti-cancer therapy. We hypothesize that grape seed procyanidin extract (GSE) exerts antineoplastic effects through modulations of oncomirs and their downstream targets. We found that GSE significantly down-regulated oncomirs miR-19a and -19b in a variety of lung neoplastic cells. GSE also increased mRNA and protein levels of insulin-like growth factor II receptor (IGF-2R) and phosphatase and tensin homolog (PTEN), both predicted targets of miR-19a and -19b. Furthermore, GSE significantly increased PTEN activity and decreased AKT phosphorylation in A549 cells. Transfection of miR-19a and -19b mimics reversed the up-regulations of IGF2R and PTEN gene expression and abrogated the GSE induced anti-proliferative response. Additionally, oral administration of leucoselect phytosome, comprised of standardized grape seed oligomeric procyanidins complexed with soy phospholipids, to athymic nude mice via gavage, significantly down-regulated miR-19a, -19b and the miR-17-92 cluster host gene (MIR17HG) expressions, increased IGF-2R, PTEN, decreased phosphorylated-AKT in A549 xenograft tumors, and markedly inhibited tumor growth. To confirm the absorption of orally administered GSE, plasma procyanidin B1 levels, between 60 and 90 min after gavage of leucoselect phytosome (400 mg/kg), were measured by LC/MS at week 2 and 8 of treatment; the estimated concentration that was associated with 50% growth inhibition (IC50) (1.3 μg/mL) in vitro was much higher than the IC50 (0.032-0.13 μg/ml) observed in vivo. Our findings reveal novel antineoplastic mechanisms by GSE and support the clinical translation of leucoselect phytosome as an anti-neoplastic and chemopreventive agent for lung cancer.

Grape Seed Procyanidin Extract Mediates Antineoplastic Effects against Lung Cancer via Modulations of Prostacyclin and 15-HETE Eicosanoid Pathways

“…Leucoselect had been shown to improve the total antioxidant capacity of plasma and reduce LDL susceptibility to oxidative stress in heavy smokers (24). As such, we evaluated its efficacy in our preclinical study, using an A549 lung cancer xenograft nude mouse model, and demonstrated significant efficacy in tumor growth inhibition (25). These findings set the stage for our lung cancer chemoprevention trial with leucoselect phytosome.…”

Genetic variants in MIR17HG affect the susceptibility and prognosis of glioma in a Chinese Han population

“…Functional studies have con rmed that the MIR17HG gene might be related to cell survival, proliferation, differentiation, and angiogenesis [10]. LncRNA MIR17HG, also as a long noncoding RNA which regulating the expression of miRNA, played a carcinogenic effect in various cancers including rectal cancer, gastric cancer, and lung cancer [11][12][13]. A recent research showed that lncRNA MIR17HG was overexpressed in glioma, and lncRNA MIR17HG knockdown inhibited the proliferation, migration and invasion of glioma, suggesting that lncRNA MIR17HG might facilitate the malignant progress of glioma [14].…”

Procyanidins Mitigate Osteoarthritis Pathogenesis by, at Least in Part, Suppressing Vascular Endothelial Growth Factor Signaling

“…For example, reduction of symptoms have been documented with the use of curcumin [16], extract of green tea [17], and extra virgin olive oil [18]. As a part of this group of generally recognized as safe (GRAS) plant-based products, procyanidins are a family of plant metabolites found in fruits, vegetables, nuts, seeds, flowers, and bark that have been shown to have beneficial biological activities, including anti-oxidative [19,20,21], anti-cancer [22,23,24], and vasorelaxing effects [25,26,27]. The composition of procyanidins include catechin, epicatechin, procyanidins B1–B5 and procyanidin C1 [28].…”