# Combinations of Grape Seed and Milk Thistle Extracts Against Lung

> **NIH VA I01** · ALBUQUERQUE VA MEDICAL CENTER · 2020 · —

## Abstract

Grape seed procyanidin extract (GSE), and milk thistle silymarin extract (MTE) are widely used health food
supplements to promote cardiovascular (CV) and hepatobiliary health, respectively. Both GSE and MTE
contain high levels of polyphenols that are structurally distinct with strong antioxidant properties, and each
agent has been shown to exert antineoplastic effects against lung cancer. Preliminary data using combinations
of GSE and MTE shows exciting, unequivocal synergistic anticancer effects against lung pre- and cancer cells
in vitro. We therefore hypothesize that oral administration of combinations of leucoselect phytosome (LP), a
standardized GSE, and siliphos, a standardized MTE, both complexed with soy phospholipids into phytosomes
to enhance bioavailability, will synergistically inhibit lung cancer growth, invasion, and induce apoptosis in
various human lung cancer xenograft models, via favorable modulations of mechanisms associated with lung
tumorigenesis/promotion. To test these hypotheses, we will determine their pharmacokinetics (PK) and
pharmacodynamics (PD). We will also determine the utility of biospecimens, such as snap, fresh frozen lung
tissue homogenates, as surrogate model systems to monitor the bioavailability and bioactivity of oral
administration of these agents to the target organ. Furthermore, the mechanistic effects of the combinations
will be assessed systematically with cancer relevant, pathway specific gene expressions and microRNA
(miRNA) real time PCR arrays, and correlated to functional significance. Three specific aims are proposed:
Aim 1: To determine the maximum tolerated dose (MTD), PK/PD, and anti-cancer effects of LP with siliphos
in murine models. A dose range finding study will be conducted in nude mice given varying dose combinations
via oral gavage to establish MTD. Blood and lung samples will be obtained to determine PK of GSE, MTE and
metabolites as surrogate markers of bioavailability of GSE and MTE. Aim 1.1. To determine the bioactivity of
oral LP and siliphos using a novel co-culture system of frozen mouse lung homogenates with human lung
neoplastic cells. Bioactivity in the lungs will be assessed by co-culturing lung tissue homogenates from control
(water) vs. drug treated mice with human lung cancer and precancerous cell lines. The effects of varying dose
combinations on proliferation and apoptosis in co-cultured cells will be correlated to GSE, MTE and metabolites
levels. Aim 2: To determine the anti-cancer effects of combinations of LP and siliphos on various types of
human lung cancer xenograft mouse models. Based on MTD findings, varying dose combinations will be given
via oral gavage to mice bearing a variety of human lung tumor xenografts for up to 8 weeks with serial
collections of plasma, lung tissues and tumor xenografts from each treatment group. The anticancer effects
will be determined by tumor growth delay or time to reach maximum tumor volume, as well as proliferation (Ki-
67) and ...

## Key facts

- **NIH application ID:** 9815335
- **Project number:** 5I01BX004092-02
- **Recipient organization:** ALBUQUERQUE VA MEDICAL CENTER
- **Principal Investigator:** JENNY T MAO
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-10-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9815335

## Citation

> US National Institutes of Health, RePORTER application 9815335, Combinations of Grape Seed and Milk Thistle Extracts Against Lung (5I01BX004092-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9815335. Licensed CC0.

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