Amygdalin influences bladder cancer cell adhesion and invasion in vitro.

Jasmina Makarević,Igor Tsaur,Eva Juengel,Axel Haferkamp,Jochen Rutz,Roman A Blaheta,Silke Kaulfuss,Jesco Pfitzenmaier,Karen Nelson,Zoran Culig

doi:10.1371/journal.pone.0110244

Jasmina Makarević, Igor Tsaur + Show 8 more

Open Access

https://doi.org/10.1371/journal.pone.0110244

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Abstract

The cyanogenic diglucoside amygdalin, derived from Rosaceae kernels, is employed by many patients as an alternative anti-cancer treatment. However, whether amygdalin indeed acts as an anti-tumor agent is not clear. Metastasis blocking properties of amygdalin on bladder cancer cell lines was, therefore, investigated. Amygdalin (10 mg/ml) was applied to UMUC-3, TCCSUP or RT112 bladder cancer cells for 24 h or for 2 weeks. Tumor cell adhesion to vascular endothelium or to immobilized collagen as well as tumor cell migration was examined. Effects of drug treatment on integrin α and β subtypes, on integrin-linked kinase (ILK) and total and activated focal adhesion kinase (FAK) were also determined. Integrin knock-down was carried out to evaluate integrin influence on migration and adhesion. A 24 h or 2 week amygdalin application distinctly reduced tumor cell adhesion and migration of UMUC-3 and RT112 cells. TCCSUP adhesion was also reduced, but migration was elevated under amygdalin. Integrin subtype expression was significantly and specifically altered by amygdalin depending on the cell line. ILK was moderately, and activated FAK strongly, lost in all tumor cell lines in the presence of amygdalin. Knock down of β1 integrin caused a significant decrease in both adhesion and migration of UMUC-3 cells, but a significant increase in TCCSUP adhesion. Knock down of β4 integrin caused a significant decrease in migration of RT112 cells. Since the different actions of amygdalin on the different cell lines was mirrored by β1 or β4 knock down, it is postulated that amygdalin influences adhesion and migratory properties of bladder cancer cells by modulating β1 or β4 integrin expression. The amygdalin induced increase in TCCSUP migratory behavior indicates that any anti-tumor benefits from amygdalin (seen with the other two cell lines) may depend upon the cancer cell type.

Highlights

The use of complementary and alternative medicine (CAM) has steadily increased over the past decades
Amygdalin significantly reduced attachment of all three bladder cancer cell lines to HUVEC when compared to untreated cells
Cell adhesion of TCCSUP and RT112 was more strongly altered by amygdalin than that of UMUC-3 cells

Summary

Introduction

The use of complementary and alternative medicine (CAM) has steadily increased over the past decades. The consumption of natural products is most wide spread. Up to 80% of cancer patients in the United States [2], and more than 50% of cancer patients in Europe use CAM together with or in place of conventional therapy [3]. Dissatisfaction with conventional treatment and reduction of chemotherapeutic side effects are the most commonly given reasons for the use of CAM [4,5]. In contrast to the wide spread use of natural compounds, information about their therapeutic effectivity is sparse. Since the 1920s, amygdalin has been orally applied to treat cancer patients in the United States. In the 1950s, an intravenous form of amygdalin was synthesized and patented as laetrile [6].

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