Amygdalin Blocks Bladder Cancer Cell Growth In Vitro by Diminishing Cyclin A and cdk2

Abstract

Amygdalin, a natural compound, has been used by many cancer patients as an alternative approach to treat their illness. However, whether or not this substance truly exerts an anti-tumor effect has never been settled. An in vitro study was initiated to investigate the influence of amygdalin (1.25–10 mg/ml) on the growth of a panel of bladder cancer cell lines (UMUC-3, RT112 and TCCSUP). Tumor growth, proliferation, clonal growth and cell cycle progression were investigated. The cell cycle regulating proteins cdk1, cdk2, cdk4, cyclin A, cyclin B, cyclin D1, p19, p27 as well as the mammalian target of rapamycin (mTOR) related signals phosphoAkt, phosphoRaptor and phosphoRictor were examined. Amygdalin dose-dependently reduced growth and proliferation in all three bladder cancer cell lines, reflected in a significant delay in cell cycle progression and G0/G1 arrest. Molecular evaluation revealed diminished phosphoAkt, phosphoRictor and loss of Cdk and cyclin components. Since the most outstanding effects of amygdalin were observed on the cdk2-cyclin A axis, siRNA knock down studies were carried out, revealing a positive correlation between cdk2/cyclin A expression level and tumor growth. Amygdalin, therefore, may block tumor growth by down-modulating cdk2 and cyclin A. In vivo investigation must follow to assess amygdalin's practical value as an anti-tumor drug.

Inhibition of cell growth and down-regulation of telomerase activity by amygdalin in human cancer cell lines

“…Moreover, our results showed that the amygdalin is efficiently induced to the inhibition of cell growth at ∼10 mg/ml concentration as reported in the previous studies (Shragg et al 1982;Chen et al 2013;Makarević et al 2014aMakarević et al , 2014b. However, we interestingly found that the normal somatic cells (MCR-5 fibroblasts) show considerable resistance to the cell growth and senescence at 10 mg/ml concentration of amygdalin.…”

“…a, b, c and d indicate significant (P < .05) difference among untreated control cell lines, * indicates significant (P < .05) difference between control and 10 mg/ml amygdalintreated cell lines, respectively. modulating β1 or β4 integrin expression (Makarević et al 2014b). These results suggest that amygdalin induces cell cytotoxicity by interfering with the progression of the cell cycle and inducing apoptosis.…”

“…Amygdalin, sometimes known as laetrile or vitamin B17, is one of the natural cyanogenic diglucoside existing in the fruits and nuts, such as cherries, apricots kernels, apples and almonds (Holzbecher et al 1984;Santos Pimenta et al 2014). It has been previously reported that amygdalin treatment in human cancer cells exerts a potential cytotoxic and anti-cancer effects by inducing apoptotic cell death (Syrigos et al 1998;Chang et al 2006;Chen et al 2013), arrest cell cycle through downregulation of cell cycle-related genes (Park et al 2005;Makarević et al 2014a) and blocking metastasis that can lead to the spread of cancer to other tissues (Makarević et al 2014b). Primarily, cancer has been treated by using conventional therapies; however, amygdalin is also used as an alternative medicine and was found one of the most useful and effective alternative in cancer therapy (Milazzo et al 2007;Sauer et al 2015).…”

Stimulatory Effect of Amygdalin on the Viability and Steroid Hormone Secretion by Porcine Ovarian Granulosa Cells in Vitro

“…In the late 1970s and early 1980s, amygdalin was reported to selectively kill cancer cells at the tumor site without systemic toxicity and to effectively relieve pain in cancer patients (Ellison et al, 1978). Nowadays, there are statistics described that by 1978 more than 70,000 patients with cancers in the United States have been treated with amygdalin (Moss, 2005;Makarević et al, 2014;Qian et al, 2015). However, the use of the drug was discouraged when it was demonstrated that amygdalin is metabolized in the body to release significant amount of cyanide thus leading to cyanide poisoning (Chandler et al, 1984;Bromley et al, 2005).…”

“…Numerous studies have demonstrated the beneficial properties of amygdalin and its ability to effectively induce cell death (Zhou et al, 2012;Chen et al, 2013). Nevertheless, proponents consider amygdalin a natural cancer cure, whereas opponents warn that amygdalin is ineffective and even toxic (Makarević et al, 2014). The endocrine signaling molecules represent source of communication between several organs, as well as specific cell populations.…”