# Mistletoe Extracts Inhibit Progressive Growth of Prostate Cancer Cells

## TL;DR

Mistletoe extracts from different host trees inhibit the growth and spread of prostate cancer cells in lab tests, suggesting potential as a complementary treatment.

## Contribution

The study identifies specific mistletoe extracts that inhibit prostate cancer cell growth and explores their molecular mechanisms.

## Key findings

- Mistletoe extracts significantly inhibited prostate cancer cell growth and proliferation in a dose-dependent manner.
- Populi and Salicis extracts induced G2/M cell-cycle arrest and increased apoptosis in cancer cells.
- Mistletoe extracts down-regulated CDK1, cyclin A, and integrin receptors, affecting cancer cell survival.

## Abstract

Although multimodal therapeutic management has significantly improved outcome in prostate cancer (PCa) patients, treatment options for castrate-resistant disease remain challenging. Plant-derived mistletoe extracts have supported cancer patients and are, therefore, widely used as complementary medicine. However, mechanisms behind possible mistletoe benefits to PCa patients remain to be explored. The present study was designed to evaluate the effect of mistletoe extracts from four different host trees (Tiliae, Populi, Salicis, and Crataegi) on the growth and proliferation of PCa cell lines in vitro. PC3, DU145, and LNCaP cells were used to evaluate tumor cell growth (MTT assay) and proliferation (BrdU incorporation assay). Clonogenicity, apoptosis, cell cycle, and cell-cycle-regulating proteins (cyclin-dependent kinases (CDKs) and cyclins) were investigated, as was CD44 standard and splice variant expression and integrin α and β receptors. SiRNA knockdown studies were employed to investigate the functional relevance of integrins. All mistletoe extracts significantly inhibited cell growth in a dose-dependent manner and cell proliferation and clonogenicity were suppressed. Populi and Salicis induced cell-cycle arrest in the G2/M phase and increased apoptosis. Both extracts down-regulated CDK1 and cyclin A and altered CD44 expression. Integrins α5 in all cell lines and α6 in DU145 and LNCaP were particularly diminished. Knocking down α5 and α6 induced cell growth inhibition in DU145. Mistletoe extracts block the growth and proliferation of PCa cells in vitro and therefore qualify for use in future animal studies to evaluate mistletoe as an adjunct to standard PCa treatment.