Breast cancer is most common in women in the world and in Turkey and that is the most common cause of cancer death. According to the 2018 data of IARC (International Agency for Research on Cancer) affiliated to the WHO (World Healt Organization), the number of newly diagnosed breast cancer patients worldwide is 2,000,088, and the difference between lung cancer, the most common cancer, is only 5.000 is up [12]. The incidence of breast cancer in Turkey 50 / 100,000 is above is calculated as the number of patients newly diagnosed 22,500 in 2018 [12, 19].
The incidence of breast cancer in Turkey, in a study published in 1994, 24 / 100,000 is designated as (Fidaner et al., 2001). In the past 25 years, the incidence of breast cancer has increased approximately 2.5 times [12, 19]. The reasons for this increase are: 1) Change in lifestyle (obesity, inactivity, not giving birth, late birth > 35 years), short-term lactation, early menarche, late menopause, long-term contraceptive pill and menopause treatment, etc.), 2) The aging of the population. 3) Awareness (warnings from the media, information and referrals for screening mammography in breast and menopause polyclinics, increase in the knowledge and education level of women, etc.), increase in the number of irregular mammography and 4) increase in the population. This rapid increase in the frequency of breast cancer in our country, prevention, requires serious work for screening and early diagnosis. For these reasons, much research is needed on new drug designs and the applicability of these drugs. In this study, it was aimed to highlight the binding mechanisms of amygdalin to BRCA-1 and BRCA-2 genes used in the diagnosis of breast cancer, and to reveal its suitability for use in in vivo and in vitro studies on breast cancer.
Until now, the exact cause of breast cancer has not been determined, and various genetic and environmental factors are involved in its development. Genetic mutations in some genes such as BRCA1, BRCA2, TP53, CDH1, MRE11A, NBN, PALB2, PTEN, RAD50, RECQL, RINT1, CHEK2, 1 and Survivin increase the development of breast cancer. Any abnormality in these genes increases the detection of breast cancer by testing [20, 21].
According to the studies carried out, it has been argued that amygdalin taken by natural means will increase its effect according to the method of application. As an example, Jaswal et al. showed that the amount of hydrogen cyanide produced by natural ingestion of amygdalin is different depending on the intestinal microbes that hydrolyze amygdalin. In the study conducted by Moertel et al., it was not observed that intravenous infusion of amygdalin into the human body caused neither cyanidemia nor toxicity symptoms [22, 23].
Makarevic et al. examined the levels of cyclin A, cyclin B and cyclin D proteins controlling the cell cycle by applying amygdalin to cancer patients for 14 days. It has seen that the levels of these proteins that control cell turnover decrease. As a result, amygdalin plays a regulatory role in the cell cycle by controlling the suppression of proteins that regulate the cell cycle. With this study, it was determined that it has anticancer activity [24].
Hill et al. reported that amygdalin was ineffective in treatment against B16 melanoma and BW5147 AKR leukemia [25]. However, Fukuda et al. found that amygdalin has tumor growth inhibitory and protective effects against tumor formation [26]. Following oral administration of amygdalin, prunacin, glucose, mandelonitrile, benzaldehyde, and HCN are released as a result of extensive hydrolysis by emulsin enzyme (Suchard et al., 1998) or β-glycosidase enzyme [27], which is present in the gastrointestinal system and synthesized by the bacteria therein [28]. The target enzyme that cyanide acts on is cytochrome oxidase, which is the terminal oxidase of mitochondrial oxygenated respiratory chain, and as a result of its inhibition, histotoxic anoxia occurs in cells [29]. The mechanism that comes into play endogenously to remove cyanide from the body is the conversion of cyanide to thiocyanate, a relatively less toxic compound, via the mitochondrial enzyme rhodonase [30], and its excretion in urine [31]. The rhodonase enzyme may be functional in the presence of sulfur groups [32] and therefore thiosulfate, a sulfur source, is used in the treatment of cyanide poisoning. Another substance used as an antidote is sodium nitrite. It is aimed to form methemoglobin by binding nitrites to hemoglobin and to selectively bind to methemoglobin by separating cyanide from cytochrome oxidase [33].
Amygdalin has been found to induce programmed cell death (apoptosis) in human prostate cancer cells (DU145 and LNCap) [34]. Park et al. in the study conducted by [35], it has been reported that amygdalin has an anti-carcinogenic effect by damaging the DNA involved in the cycle of human colon cancer cells and therefore can be used as a cancer drug. In addition, Makarević et al. in the study conducted by [24], it was found that amygdalin showed a significant anti-tumor activity on prostate cancer cells, and therefore, it was stated that more studies are needed on its use for therapeutic purposes.
In his literature review, [36] concluded that amygdalin has a positive effect in the treatment of arteriosclerosis and diabetes, and in the prevention of cancer formation. On the other hand, it has been determined that amygdalin does not show an anticarcinogenic effect and some of its degradation products have such activity [37]. It was stated by [38] that amygdalin is effective on tumor cells, but there is not enough study on its mechanism of action. Amygdalin has been found to damage bull semen cells depending on the dose used [39]. There are no convincing data showing that amygdalin prevents rapid and distinct tumor development, especially in patients with advanced disease, however, it has been stated that the therapeutic effect of amygdalin needs to be clarified [40].
As can be understood from the literature information, it has not been clarified yet whether amygdalin has therapeutic properties. Discussions and research on the subject are ongoing. Although the issue has not been clarified, amygdalin tablets are still commercially available as natural dietary supplements under the names "laetrile" or vitamin "B17" [11]. Today, many websites sell amygdalin and many doctors use amygdalin for treatment [40].