Green Synthesis of Silver Nanoparticles Using Annona muricata Extract as an Inducer of Apoptosis in Cancer Cells and Inhibitor for NLRP3 Inflammasome via Enhanced Autophagy

Abstract

Annona muricata is one of the most important traditional medicinal plants which contains numerous chemicals that exhibit various pharmacological properties. In this study, silver nanoparticles were prepared using A. muricata peel extract as a reducing agent and the effect was enhanced through A. muricata like pharmaceutical activity. AgNPs formation was confirmed by color changes, UV-visible spectroscopy, SEM, DLS, and XRD. The anti-proliferative activity of AgNPs against THP-1, AMJ-13, and HBL cell lines was studied. Apoptotic markers were tested using AO/EtBr staining assay, cell cycle phases using flowcytometry, and the expression of P53. Autophagy takes an essential part in controlling inflammasome activation by primary bone marrow-derived macrophages (BMDMs). We report novel functions for AgNPs-affected autophagy, represented by the control of the release of IL-1β, caspase-1, adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC), and NLRP3 in BMDMs following treatment with LPS+ATP. The current study revealed that the AgNPs inhibited THP-1 and AMJ-13 cell proliferation. Meanwhile, the AgNPs significantly increased autophagy and reduced IL-1b and NLRP3 levels in both in vivo and in vitro models. The secretion of IL-1β was reduced whereas the degradation of NLRP3 inflammasome was enhanced. These findings propose that AgNPs apply an anti-proliferative activity against THP-1 and AMJ-13 cells through the stimulation of apoptosis via mitochondrial damage and induction of p53 protein pathway. In addition, AgNP-induced autophagy reduced the levels of IL-1β and NLRP3 inflammasome activation. This indicated that the AgNPs augment autophagy controlled by the IL-1β pathway via two different novel mechanisms. The first one is regulating activation of the IL-1 β, caspae-1, and ASC, while the second is NLRP3 targeting for lysosomal degradation. Overall, this study suggests that AgNPs could be a potent therapy for various types of cancer and an alternative treatment for preventing inflammation via enhancing autophagy.

Silver Nanoparticles from Annona muricata Peel and Leaf Extracts as a Potential Potent, Biocompatible and Low Cost Antitumor Tool

“…Moreover, cells presented a “flat surface” due to the loss of microvilli and filopodia structures and the apparition of apoptotic bodies a clear signal of death by apoptosis ( Figure 6 ). These results are in concordance with those reported by Jabir and collaborators in THP-1 and AMJ-13 cell lines [ 53 ].…”

“…In addition, the IC 50 obtained have been much lower than those described in the literature since with an IC 50 of only 1.685 µg/mL, our AgNPs-PE from A. muricata were able to induce cytotoxicity to MDA-MB-468, a triple negative breast cancer cell line (do not express estrogen receptor (ER), progesterone receptor (PR), and do not have HER-2/Neu amplification), characterized by a poor outcome compared to the other subtypes of breast cancer [ 52 ]. To the best of our knowledge, the only study that analyzes the antitumor effect of AgNPs-PE from A. muricata was in an AMJ-13 breast cancer cell line (ER − ,PR − and HER2/neu + ) and reported an IC 50 of 17.34 µg/mL using AgNPs synthetized from A. muricata stock solution 10-fold more concentrated than ours [ 53 ]. This could be due to the geographical origin of the plant, the season in which both the leaves and the peel of the fruit were collected and even its age [ 54 , 55 , 56 ].…”

Green Synthesis of Silver Nanoparticles Using the Flower Extract of Abelmoschus esculentus for Cytotoxicity and Antimicrobial Studies

“…As a result, the pro-apoptotic mitochondrial protein Cyt C is released into the cytosol and induces apoptosis by activating the apoptotic proteins caspase-9 and caspase-3. [57][58][59][60]…”

Anticariogenic Effect of Selenium Nanoparticles Synthesized Using Brassica oleracea

“…Besides, in the conventional process, the form, size, and instability of the synthesized particle are the main limitations [10]. This creates a great desire to synthesize nanoparticles with harnessed size and nanometer morphology in an eco-friendly mode [11]. The size and the shape of nanoparticles are permanently related to the unique characteristics, work, and application of nanomaterials [12,13].…”