<p>Magnetically Directed Enzyme/Prodrug Prostate Cancer Therapy Based on β-Glucosidase/Amygdalin</p>

Abstract

Background: β-Glucosidase (β-Glu) can activate amygdalin to kill prostate cancer cells, but the poor specificity of this killing effect may cause severe general toxicity in vivo, limiting the practical clinical application of this approach. Materials and Methods: In this study, starch-coated magnetic nanoparticles (MNPs) were successively conjugated with β-Glu and polyethylene glycol (PEG) by chemical coupling methods. Cell experiments were used to confirm the effects of immobilized β-Glu on amygdalin-mediated prostate cancer cell death in vitro. Subcutaneous xenograft models were used to carry out the targeting experiment and magnetically directed enzyme/prodrug therapy (MDEPT) experiment in vivo. Results: Immobilized β-Glu activated amygdalin-mediated prostate cancer cell death. Tumor-targeting studies showed that PEG modification increased the accumulation of β-Glu-loaded nanoparticles in targeted tumor tissue subjected to an external magnetic field and decreased the accumulation of the nanoparticles in the liver and spleen. Based on an enzyme activity of up to 134.89 ± 14.18mU/g tissue in the targeted tumor tissue, PEG-β-Glu-MNP /amygdalin combination therapy achieved targeted activation of amygdalin and tumor growth inhibition in C57BL/6 mice bearing RM1 xenografts. Safety evaluations showed that this strategy had some impact on liver and heart function but did not cause obvious organ damage. Conclusion:All findings indicate that this magnetically directed enzyme/prodrug therapy strategy has the potential to become a promising new approach for targeted therapy of prostate cancer.

In Vivo Growth Inhibition of Human Caucasian Prostate Adenocarcinoma in Nude Mice Induced by Amygdalin with Metabolic Enzyme Combinations

“…The first objectives of this research was to verify the concept that amygdalin triggers growth inhibition in human prostate cancer cell line PC3 cells in vivo and to analyze its metabolic enzymes rhodanese and betaglucosidase as a potential adjunct to the existing prostate cancer therapy regimen ( Figure 5 ). In in vivo, amygdalin injection reduced tumour development in PC3 cells through an apoptotic mechanism induced by betaglucosidase activation [ 32 , 33 ]. According to specific research, cancer cells have a high concentration of betaglucosidase, which may be used to break down amygdalin and produce cyanide, which is harmful to cancer cells.…”

“…In contrast, malignant cells lack RHD, and so the creation of HCN is stored in these cells [ 18 , 28 – 30 ]. AMD may have a therapeutic impact on prostate cancer by inhibiting the viability of PC3 cells in vitro [ 17 , 31 , 32 ]. Additionally, no report of the same outcomes in vivo has been recorded.…”

The Multiple Actions of Amygdalin on Cellular Processes with an Emphasis on Female Reproduction

“…Amygdalin possesses therapeutic effect against atherosclerosis [9], in the management of autoimmune hepatitis [54], and anti-tumor effects against various cell lines [13,16,25,35,41,[55][56][57]. This phytocompound can affect the cell cycle of cancer cells, reduce cell cycle activators, especially cyclin B, cdk1, E-cadherin, and N-cadherin and activate multiple cellular pathways, inhibit the Akt-mTOR signaling pathway thereby inhibiting the proliferation of cancer cells [45,56,58].…”

Amygdalin as a Plant-Based Bioactive Constituent: A Mini-Review on Intervention with Gut Microbiota, Anticancer Mechanisms, Bioavailability, and Microencapsulation

“…This inspires further in vivo analysis of the prepared amygdalin-loaded ACNPs on cancer tumor models. Recently, Zhou et al [42] showed that by chemical coupling methods, starch-coated magneticiinanoparticles (MNPs) were successively conjugated with β-glucosidase (β-Glu) iand polyethylene glycol (PEG). Consequently, amygdalinmediatediimmobilized β-Glu activatediprostate cancer cell death.…”