Amygdalin Blocks Bladder Cancer Cell Growth In Vitro by Diminishing Cyclin A and cdk2
Jasmina Makarević,
Jochen Rutz,
Eva Juengel,
Silke Kaulfuss,
Michael Reiter,
Igor Tsaur,
Georg Bartsch,
Axel Haferkamp ,
Roman A. Blaheta mail
Introduction
Bladder carcinoma is the second most common malignancy of the genitourinary tract in western countries, with an incidence of 37.9/100,000 per year for men and 9.6/100,000 per year for women
[1]. Approximately 70% of initially diagnosed tumors are superficial and can be treated by transurethral resection, whereby the bladder is preserved. The remaining 30% of tumors become muscle invasive and are associated with a high risk of metastasis
[2]. For those patients with locally advanced or metastatic disease, chemotherapy is a treatment option. However, the prognosis of patients with metastases remains poor, with a median survival of 14 months and a 5-year survival rate of 15%
[3].
More than 50% of cancer patients in Europe use complementary/alternative medicine (CAM) instead of, or combined with, conventional therapy
[4]. Dissatisfaction with conventional treatment and reduction of chemotherapeutic side effects are the most common reasons given for the use of CAM
[5],
[6]. However, although CAM usage is popular among cancer patients, evidence based benefit from naturally based compounds is lacking. The discrepancy between use of a natural product and knowledge about its anti-tumor properties is notably reflected in the case of amygdalin. Amygdalin (D-mandelonitrile-β-gentiobioside) is a cyanogenic diglucoside present in the pits of many fruits and in numerous plants belonging to the Rosaceae family such as Prunus persica (peach), Prunus armeniaca (apricot) and Prunus amygdalus amara (bitter almond). The term “laetrile” is frequently used as a synonym for amygdalin. However, laetrile is structurally different from the mother compound, amygdalin, and is an acronym (LAEvorotatory and mandeloniTRILE) for a purified, semi-synthetic form of amygdalin. The present investigation employs “amygdalin”.
Amygdalin was one of the most popular, non-conventional, anti-cancer treatments in the 1970s. By 1978, 70,000 US cancer patients had used amygdalin to treat their cancer
[7]. Still, evidence based research on amygdalin is sparse and its benefit controversial. Proponents consider amygdalin a natural cancer cure, whereas opponents warn that amygdalin is ineffective and even toxic. Although it has been argued that amygdalin is unsafe, no serious acute toxicity has been encountered. It has also been concluded that amygdalin has no anti-tumor potential, although from 368 cancer patients listed in one review, 12.5% experienced a complete or partial response, 6.8% had stable disease and 22.9% demonstrated symptomatic benefit from amygdalin
[8]. To gain insight into how amygdalin might function, an in vitro investigation was initiated to determine its influence on bladder cancer growth and proliferation. Additionally, cell cycle progression and cell cycle regulating proteins were evaluated in amygdalin treated and non-treated cells. siRNA knock down studies were carried out to explore proteins altered by amygdalin, which may have clinical relevance.
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