Oncotarget

Research Papers:

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

Bingye Xue, Qing-Yi Lu, Larry Massie, Clifford Qualls and Jenny T. Mao _

PDF  |  HTML  |  How to cite  |  Order a Reprint

Oncotarget. 2018; 9:15579-15590. https://doi.org/10.18632/oncotarget.24528

Metrics: PDF 805 views  |   HTML 1972 views  |   ?  


Abstract

Bingye Xue1, Qing-Yi Lu2, Larry Massie3, Clifford Qualls4 and Jenny T. Mao1

1Pulmonary, Critical Care, and Sleep Section, New Mexico Veterans Administration Health Care System, University of New Mexico, Biomedical Research Institute of New Mexico, Albuquerque, NM, USA

2UCLA Center for Human Nutrition, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

3Pathology and Clinical Laboratory Services, New Mexico Veterans Administration Health Care System, University of New Mexico, Albuquerque, NM, USA

4Biomedical Research Institute of New Mexico, New Mexico Veterans Administration Health Care System, University of New Mexico, Albuquerque, NM, USA

Correspondence to:

Jenny T. Mao, email: jenny.mao@va.gov

Keywords: oncomir; P21; CDKN1A; pharmacokinetics; pharmacodynamics

Received: July 23, 2017     Accepted: February 10, 2018     Epub: February 16, 2018     Published: March 20, 2018

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 24528