Full length articleAmygdalin delays cell cycle progression and blocks growth of prostate cancer cells in vitro
Introduction
In 2015, 220 800 new cases of prostate cancer (PCa) were estimated to occur in the US while 27 540 males would succumb, making PCa, besides skin cancer, the most frequently diagnosed malignancy and the second leading cause of cancer death in men [1]. The exceptional clinical and economic significance of PCa has contributed to much research, promoting rapidly expanding treatment options for metastatic PCa [2]. Thus, significant survival improvement in the castration-resistant stage has been achieved through clinical application of novel androgen biosynthesis and receptor targeting drugs, radiopharmaceuticals, cytoreductive and immunotherapeutic agents [3]. Preliminary data also point to a promising outcome of early docetaxel chemotherapy in castration-sensitive PCa, although further evaluation is warranted for this therapeutic concept [4]. Despite encouraging results of new protocols, primary or acquired drug resistance precludes long-term response. Cross-resistance often restricts the efficacy of subsequent therapy [5]. In addition, adverse effects, necessitating close patient monitoring and even treatment interruption, may limit clinical application [6].
To avoid toxicity, boost the immune system and possibly prevent PCa recurrence [7], growing popularity for complementary and alternative medicine (CAM) has occurred, despite scarce evidence-based efficacy [8]. About one third of patients with PCa, and even more with advanced disease, utilize CAM in the form of natural health products such as vitamin E, saw palmetto, selenium and lycopene [9], [10]. Due to reported antitumor activity the cyanogenic substance, diglucoside amygdalin (d-mandelonitrile-β-gentiobioside), has been used as a synergistic partner with established agents to treat PCa. The substance, abundant in fruit kernels from Rosaceae species is hoped to help avert negative effects of chemotherapy [11]. However, the impact of amygdalin on PCa and its molecular mechanism of activity remain to be clarified.
The aim of the current study was, therefore, to investigate the effects of amygdalin on the growth capacity and molecular machinery in three PCa cell lines.
Section snippets
Cell culture
Human prostate tumor cell lines PC3, DU-145 (castration-resistant) and LNCaP (castration-sensitive) were obtained from DSMZ (Braunschweig, Germany). Tumor cells were grown and subcultured in RPMI 1640 (Gibco/Invitrogen; Karlsruhe, Germany). The medium contained 10% fetal calf serum (FCS), 2% HEPES-buffer (1 M, pH 7.4), 2% glutamine and 1% penicillin/streptomycin.
Amygdalin treatment
Amygdalin from apricot kernels (Sigma-Aldrich, Taufkirchen, Germany) was freshly dissolved in cell culture medium (1–10 mg/ml) and
Dose–response analysis
Exposing PC3, DU-145 and LNCaP tumor cells to amygdalin for 24 h led to a concentration-dependent reduction in tumor cell number, with the most prominent effects apparent in the presence of 10 mg/ml (Fig. 1A, 24 h incubation). The same response was seen when tumor cells were chronically treated with amygdalin for 2 weeks (Fig. 1A, 2 weeks incubation). The trypan blue exclusion test revealed no toxic effects to the tumor cell lines following exposure to 10 mg/ml amygdalin (data not shown). Since the
Discussion
This investigation demonstrates that amygdalin treatment significantly reduces the growth rate of both castration-sensitive (LNCaP) and castration-resistant (PC3, DU-145) cell lines and attenuates clone formation in all three cell lines, without toxic effects. These findings agree with reports showing growth-inhibiting, anti-proliferative and pro-apoptotic effects of amygdalin on promyelocytic leukemia [12], colon cancer [13] cervical cancer [14] and bladder cancer cells [15]. In the present
Conclusion
These findings indicate noteworthy antineoplastic activity of the natural compound, amygdalin, in both castration-sensitive and castration-resistant PCa cells. Further validation of these preliminary data is warranted in vitro and in vivo to clarify whether amygdalin merits evaluation in properly designed future clinical trials.
Conflict of interest statement
The authors declare that there are no conflicts of interest.
Acknowledgments
This work was supported by the “Brigitta & Norbert Muth Foundation” and the “Vereinigung von Freunden und Förderern der Goethe-Universität”.
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