Targeting Proteolysis with Cyanogenic Glycoside Amygdalin Induces Apoptosis in Breast Cancer Cells

Abstract

Background: Breast cancer is the most diagnosed cancer among women, and its incidence and mortality are rapidly growing worldwide. In this regard, plant-derived natural compounds have been shown to be effective as chemotherapeutic and preventative agents. Apricot kernels are a rich source of nutrients including proteins, lipids, fibers, and phenolic compounds and contain the aromatic cyanogenic glycoside amygdalin that has been shown to exert a cytotoxic effect on cancer cells by affecting the cell cycle, inducing apoptosis, and regulating the immune function. Methods: Here, we describe a previously unexplored proapoptotic mechanism of action of amygdalin in breast cancer (MCF7) cells that involves the modulation of intracellular proteolysis. For comparative purposes, the same investigations were also conducted upon cell treatment with two apricot kernel aqueous extracts from Prunus armeniaca L. Results: We observed that both the 20S and 26S proteasome activities were downregulated in the MCF7 cells upon 24 h treatments. Simultaneously, the autophagy cascade resulted in being impaired due to cathepsin B and L inhibition that also contributed to a reduction in cancer cell migration. The inhibition of these proteolytic systems finally promoted the activation of apoptotic events in the MCF7 cells. Conclusion: Collectively, our data unveil a novel mechanism of the anticancer activity of amygdalin, prompting further investigations for potential application in cancer preventative strategies.

Amygdalin as a Promising Anticancer Agent: Molecular Mechanisms and Future Perspectives for the Development of New Nanoformulations for Its Delivery

“…Amygdalin was also found to decrease the migration of MDA-MB-231 cells more than MCF-7 cells [ 43 ]. Furthermore, the inhibition of proteolytic enzymes was suggested to promote the activation of apoptotic events in MCF-7 breast cancer cells [ 44 ]. In addition, amygdalin was shown to increase Bax and decrease Bcl-2 expression in SK-BR-3 and MCF-7 breast cancer cells.…”

Armeniacae semen amarum: a review on its botany, phytochemistry, pharmacology, clinical application, toxicology and pharmacokinetics

“…Compounds (80–84, 88–90, 94–97, 112) are flavanols. Additionally, 12 anthocyanins (99–111) have been extracted from ASA skins, which belong to flavonoids as well ( Qin et al, 2019 ; Cecarini et al, 2022 ). These flavonoids are summarized in Table 1 , and their chemical structures were drawn using ChemDraw 20.0 and presented in Figure 2 .…”

“…Furthermore, when MCF-7 breast cancer cells and MCF-10A normal cells were treated with 50 μM amygdalin and 1 mg/mL ASA extract, it was observed that the activities of proteasomes 20S and 26S, Cathepsin B, and cathepsin L in MCF-7 cells were inhibited. Additionally, the expressions of p53, p27, and Bax were increased, indicating that amygdalin and ASA extract may promote apoptosis and regulate the autophagy cascade ( Cecarini et al, 2022 ). Moreover, amygdalin can induce oxidative stress in breast cancer cells by increasing GSH activity and reducing MDA and oxidized glutathione levels, thereby exerting anti-cancer effects ( Abboud et al, 2019 ).…”

Isomerization and Stabilization of Amygdalin from Peach Kernels

“…To better illustrate the advantage of our optimized ultrasound method for extraction of amygdalin from peach kernels, we used the hot water extract method [37] (boiling water for 30 min) for comparison (Figure 7E). Using the ultrasound method, the yield of amygdalin was 1.76%.…”