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Mistletoe Extracts from Different Host Trees Disparately Inhibit Bladder Cancer Cell Growth and Proliferation
Eva Juengel1, Jochen Rutz2, Moritz Meiborg2
1Department of Urology and Pediatric Urology, University Medical Center Mainz, 55131 Mainz, Germany.
Abstract:
Extracts of European mistletoe (Viscum album) are popular as a complementary treatment for patients with many different cancer types. However, whether these extracts actually block bladder cancer progression remains unknown. The influence of different mistletoe extracts on bladder cancer cell growth and proliferation was investigated by exposing RT112, UMUC3, and TCCSup cells to mistletoe from hawthorn (Crataegi), lime trees (Tiliae), willow trees (Salicis), or poplar trees (Populi). The tumor cell growth and proliferation, apoptosis induction, and cell cycle progression were then evaluated. Alterations in integrin α and β subtype expression as well as CD44 standard (CD44s) and CD44 variant (CD44v) expressions were evaluated. Cell cycle-regulating proteins (CDK1 and 2, Cyclin A and B) were also investigated. Blocking and knock-down studies served to correlate protein alterations with cell growth. All extracts significantly down-regulated the growth and proliferation of all bladder cancer cell lines, most strongly in RT112 and UMUC3 cells. Alterations in CD44 expression were not homogeneous but rather depended on the extract and the cell line. Integrin α3 was, likewise, differently modified. Integrin α5 was diminished in RT112 and UMUC3 cells (significantly) and TCCSup (trend) by Populi and Salicis. Populi and Salicis arrested UMUC3 in G0/G1 to a similar extent, whereas apoptosis was induced most efficiently by Salicis. Examination of cell cycle-regulating proteins revealed down-regulation of CDK1 and 2 and Cyclin A by Salicis but down-regulation of CDK2 and Cyclin A by Populi. Blocking and knock-down studies pointed to the influence of integrin α5, CD44, and the Cyclin-CDK axis in regulating bladder cancer growth. Mistletoe extracts do block bladder cancer growth in vitro, with the molecular action differing according to the cell line and the host tree of the mistletoe. Integrating mistletoe into a guideline-based treatment regimen might optimize bladder cancer therapy.
Insights
European mistletoe extracts significantly inhibit bladder cancer cell growth and proliferation in vitro. The specific molecular mechanisms vary by mistletoe source and cancer cell line, highlighting potential for tailored cancer therapy.
Area of Science:
- Oncology
- Pharmacology
- Complementary and Alternative Medicine
Background:
- European mistletoe (Viscum album) extracts are widely used as complementary cancer treatments.
- The efficacy of mistletoe extracts in blocking bladder cancer progression is not well-established.
- Understanding the molecular impact of different mistletoe extracts on bladder cancer is crucial.
Purpose of the Study:
- To investigate the influence of various European mistletoe extracts on bladder cancer cell growth and proliferation.
- To evaluate the effects of mistletoe extracts on apoptosis, cell cycle progression, and specific protein expressions.
- To correlate molecular alterations with observed effects on bladder cancer cell growth.
Main Methods:
- Exposure of bladder cancer cell lines (RT112, UMUC3, TCCSup) to mistletoe extracts from hawthorn, lime, willow, and poplar trees.
- Assessment of cell growth, proliferation, apoptosis induction, and cell cycle progression.
- Analysis of integrin and CD44 subtype expression, and cell cycle-regulating proteins (CDK1, CDK2, Cyclin A, Cyclin B).
Main Results:
- All mistletoe extracts significantly reduced bladder cancer cell growth and proliferation, with strongest effects on RT112 and UMUC3 cells.
- Molecular changes, including integrin α5 and CD44 expression, varied depending on the mistletoe source and cell line.
- Willow and poplar extracts induced cell cycle arrest (G0/G1) and apoptosis, with distinct impacts on cell cycle proteins.
Conclusions:
- European mistletoe extracts demonstrate in vitro efficacy in blocking bladder cancer growth.
- The molecular mechanisms of action are diverse and depend on the specific mistletoe extract and bladder cancer cell line.
- Mistletoe extracts show promise for optimizing bladder cancer therapy when integrated into standard treatment regimens.
