Amygdalin Induces Apoptosis through Regulation of Bax and Bcl-2 Expressions in Human DU145 and LNCaP Prostate Cancer Cells

Abstract

Amygdalin (vitamin B 17 ; previously called laetrile) is one of many nitrilosides, which are natural cyanide-containing substances abundant in the seeds of prunasin family, plant such as apricots, almonds, peaches, apples, and other rosaceous plants. Among the prunasins, Armeniacae semen has been used for the treatment of asthma, bronchitis, emphysema, leprosy, colorectal cancer, leucoderma, and pain. [1][2][3] Amygdalin is composed of two molecules of glucose, one of benzaldehyde, which induces an analgesic action, and one of hydrocyanic acid, which is an anti-neoplastic compound. Apart from the above indications, amygdalin has been used to treat cancers and relieve pain. [4][5][6] In particular, D-amygdalin (D-mandelonitrile-b-D-gentiobioside) is known to exhibit selective killing effect on cancer cells. 7)Prostate cancer is one of the most common non-skin cancers in men. This malignant tumor most often arises in the outer part of the prostate, and as the tumor grows it metastasizes to the tissues around the prostate or into the seminal vesicles. 8)Apoptosis, also known as programmed cell death, occurs in several pathological situations in multicellular organisms and constitutes part of a common mechanism of cell replacement, tissue remodeling, and removal of damaged cells. Apoptosis is a complex process characterized by cell shrinkage, chromatin condensation, internucleosomal DNA fragmentation, and formation of "apoptotic bodies." 9) Two important groups of proteins involved in apoptotic cell death are the members of the Bcl-2 family 10) and a class of cysteine proteases known as caspases.11) The Bcl-2 family can be classified into two functionally distinct groups: antiapoptotic proteins and pro-apoptotic proteins. Bcl-2, an antiapoptotic protein, is known to regulate apoptotic pathways and protects against cell death. Bax, a pro-apoptotic protein of that family, is expressed abundantly and selectively during apoptosis and promotes cell death. Increasing the ratio of Bcl-2 to Bax has commonly been used to determine the induction of apoptosis in several tissues.12) The caspases are aspartate-specific cysteine proteases that have emerged as the central executioner of apoptosis. Among the caspases, activation of caspase-3 is regarded as primary mechanism of apoptosis. 11,13) Caspase-3 can be activated through cytosolic release of cytochrome c by Bax protein. 14)Numerous studies have documented that induction of apoptosis is a very important mechanism in the spontaneous regression of tumors and in the development of anti-tumor agents.15) Apoptosis of tumor cells contributes to the tumor reduction and promotes tumor regression.16) Moreover, anticancer drugs are known to induce apoptosis of tumor cells by damaging their DNA, inhibiting DNA synthesis, depleting intracellular nucleotide pool, and disrupting mitotic apparatus. 17,18) In the present study, we prepared the aqueous extract of the amygdalin from Armeniacae semen and investigated whether this extract induces apoptotic cell death in human DU145 and LNCaP p...

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

“…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).…”

“…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). The cytotoxic effects of amygdalin against cancer cells are related with the release of hydrogen cyanide (HCN), which is an antitumor compound, decomposing carcinogenic substances in the body, inhibiting cancer growth and blocking nutrient source of tumor cells (Syrigos et al 1998;Chang et al 2006). The release of HCN from amygdalin glycoside is also related with activity of β-glucosidase enzyme that catalyzes the hydrolysis of covalent bonds linking two glucose or glucose-substituted molecules (Syrigos et al 1998).…”

Ami̇gdali̇n Ve Özelli̇kleri̇

“…Amigdalinin insan prostat kanser hücrelerinde (DU145 ve LNCap) programlanmış hücre ölümünü (apoptoz) teşvik ettiği saptanmıştır [56]. Park ve ark.…”

Blood plasma levels of anterior pituitary hormones of rabbits after apricot seed exposure in vivo

“…Amygdalin, can be used for an effective prevention and treatment of human cancer (Gomez et al, 1998). However, the Food and Drug Administration (FDA) has not approved amygdalin as a cancer treatment owing to insufficient clinical evidence of its efficacy and potential toxicity (Chang et al, 2006;Kwon et al, 2010). The seed oil has been used to treat tumors, ulcers (Rieger, 2006) well as in cosmetics and as a pharmaceutical agent (laxative and expectorant).…”