Leucoselect Phytosome Modulates Serum Eicosapentaenoic Acid, Docosahexaenoic Acid, and Prostaglandin E3 in a Phase I Lung Cancer Chemoprevention Study

Authors

Jenny T. Mao, Pulmonary, Critical Care and Sleep Section, New Mexico Veterans Administration Health Care System, and University of New Mexico, Albuquerque, New Mexico. Jenny.Mao@va.gov.
Bingye Xue, Pulmonary, Critical Care and Sleep Section, New Mexico Veterans Administration Health Care System, and University of New Mexico, Albuquerque, New Mexico
Sili Fan, UC Davis Genome Center, Davis, California
Patricia Neis, Pulmonary, Critical Care and Sleep Section, New Mexico Veterans Administration Health Care System, and University of New Mexico, Albuquerque, New Mexico
Clifford Qualls, Biostatistics, Biomedical Research Institute of New Mexico, New Mexico Veterans Administration Health Care System, and University of New Mexico, Albuquerque, New Mexico
Larry Massie, Pathology and Clinical Laboratory Services, New Mexico Veterans Administration Health Care System, and University of New Mexico, Albuquerque, New Mexico
Oliver Fiehn, UC Davis Genome Center, Davis, California

Document Type

Article

Publication Date

6-1-2021

Abstract

Grape seed procyanidin extract (GSE) has been shown to exert antineoplastic properties in preclinical studies. Recently, we reported findings from a modified phase I, open-label, dose escalation clinical study conducted to evaluate the safety, tolerability, MTD, and potential chemopreventive effects of leucoselect phytosome, a standardized GSE complexed with soy phospholipids to enhance bioavailability, in heavy active and former smokers. Three months of leucoselect phytosome treatment significantly decreased bronchial Ki-67 labeling index (LI), a marker of cell proliferation on the bronchial epithelium. Because GSE is widely used as a supplement to support cardiovascular health, we evaluate the impact of oral leucoselect phytosome on the fasting serum complex lipid metabolomics profiles in our participants. One month of leucoselect phytosome treatment significantly increased eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the omega-3 polyunsaturated fatty acids (n-3 PUFA) with well-established anticancer properties. Leucoselect phytosome also significantly increased unsaturated phosphatidylcholines (PC), likely from soy phospolipids in the phytosome and functioning as transporters for these PUFAs. Furthermore, 3-month leucoselect phytosome treatment significantly increased serum prostaglandin (PG) E₃ (PGE₃), a metabolite of EPA with anti-inflammatory and antineoplastic properties. Such increases in PGE₃ correlated with reductions of bronchial Ki-67 LI (r = -0.9; P = 0.0374). Moreover, posttreatment plasma samples from trial participants significantly inhibited proliferation of human lung cancer cell lines A549 (adenocarcinoma), H520 (squamous cell carcinoma), DMS114 (small cell carcinoma), and 1198 (preneoplastic cell line). Our findings further support the potential utility of leucoselect phytosome in reducing cardiovascular and neoplastic risks in heavy former and active smokers. PREVENTION RELEVANCE: In this correlative study of leucoselect phytosome for lung cancer chemoprevention in heavy active and former smokers, we demonstrate for the first time, favorable modulations of n-3PUFA and downstream PGE₃ in fasting serum, further supporting the chemopreventive potential of leucoselect phytosome against lung cancer.

Recommended Citation

Mao JT, Xue B, Fan S, Neis P, Qualls C, Massie L, Fiehn O. Leucoselect Phytosome Modulates Serum Eicosapentaenoic Acid, Docosahexaenoic Acid, and Prostaglandin E3 in a Phase I Lung Cancer Chemoprevention Study. Cancer Prev Res (Phila). 2021 Jun;14(6):619-626. doi: 10.1158/1940-6207.CAPR-20-0585. Epub 2021 Mar 11. PMID: 33707173; PMCID: PMC8225569.