Regulation of the PI3K/AKT/mTOR signaling pathway with synthesized bismuth oxide nanoparticles from Ginger (Zingiber officinale) extract: Mitigating the proliferation of colorectal cancer cells

In order to overcome the limitations of conventional therapeutic systems in the treatment of cancer, nanoparticles (NPs) have been rapidly produced and developed as a separate treatment method for control of cancer. Synthesis of nanoparticles using plant-based materials (green synthesis), due to the easy and cost-effective synthesis, production of non-toxic, sustainable and environmentally friendly products, can be considered the most appropriate method for preparation of NPs. In this study, after synthesis of Bi₂O₃ NPs using Ginger (Zingiber officinale) root (rhizome) extract, the synthesized NPs were characterized and their potential application as selective anticancer agents against HCT116 colorectal cancer cells was evaluated through regulation of PI3K/AKT/mTOR signaling pathway, whereas the human kidney (HK-2) cells were used as normal cells. FTIR analysis showed a band at 673 cm^?1 attributed to Bi-O vibration with a fingerprint region at 1291 cm^?1 demonstrating the attachment of the organic molecules to the synthesized Bi₂O₃ NPs. UV–visible study showed a λ_max of around 268 nm, whereas XRD analysis showed eight clear peaks, demonetizing the crystalline phase of synthesized Bi₂O₃ NPs. TEM analysis showed that spherical-shaped Bi₂O₃ NPs have a size range of 20–50 nm with a man size of around 35 nm. Finally, DLS analysis determined that Bi₂O₃ NPs have a hydrodynamic size of about 71.19 nm (PDI of 0.179) and a zeta potential value of ?44.39 mV, revealing the good colloidal stability of NPs. Cellular assays (MTT, LDH, flow cytometry, and RT-qPCR) showed that synthesized Bi₂O₃ NPs selectively induced anticancer effects against HCT116 colorectal cancer cells through membrane leakage, generation of ROS, induction of apoptosis via dysregulation of Bax, Bcl-2 and caspase-3 at mRNA level mediated via regulation of PI3K/AKT/mTOR signaling pathway. In conclusion, it may be suggested that the presence study could provide useful information for the potential anticancer effects mediated by synthesized Bi₂O₃ NPs in vitro, although further studies, including in vivo studies and clinical trials, are needed to support our findings.     

Visnagin inhibits cervical cancer cells proliferation through the induction of apoptosis and modulation of PI3K/AKT/mTOR and MAPK signaling pathway

Cervical cancer, a silent killer is a second most common type of malignant tumor detected in women’s world wide. In modern medicine the usage of phytochemicals to develop drugs for treating various chronic diseases is rapidly increasing. One such phytochemical is visnagin, a furanochrome present in fruits of Ammi visnaga. We investigated the anticarcinogenic potency of visnagin against human cervical carcinoma cells. The antioxidant potency of visnagin was analyzed with FRAP assay, DPPH assay, Chemiluminscence assay and ORAC assay. The cytotoxic effect of visnagin on normal epithelial Vero cells and human cervical cancer HeLa cells were analyzed using MTT assay. The effect of visnagin on antioxidant system was examined by measuring the levels of TBARS, SOD and GSH using the colorimetric assay techniques. DCFH-DA staining, AO/EtBr staining, propidium iodide staining was performed to assess the apoptotic induction potency of visnagin against cervical cancer cells. The ability of visnagin to inhibit cancer cell migration was examined with scratch wound assay. The anticarcinogenic property of visnagin was confirmed by analyzing the gene expression of PI3K/AKT/mTOR signaling proteins and MAPK signaling proteins using qPCR analysis. Visnagin exhibited increased Trolox equivalent value in all the four antioxidant potency estimating experiments. Visnagin induced cytotoxic effect only on carcinoma cells, decreased the antioxidants and increased the generation of ROS. It also induced apoptosis and inhibited the cancer cell migration. The qPCR analysis confirms visnagin decreases the gene expression cell cycle regulating protein of both PI3K/AKT/mTOR and MAPK pathway. Overall our results authentically prove visnagin inhibits the progression of cervical cancer in vitro. Therefore it can be an ideal drug of choice which can subject to further investigation for treating cervical cancer.     

Piperine loaded zinc oxide nanocomposite inhibits the PI3K/AKT/mTOR signaling pathway via attenuating the development of gastric carcinoma: In vitro and in vivo studies

Gastric cancer (GC) is the fifth most cancer type and the third most cause of cancer-associated deaths worldwide along with the 5-year survival rate is less the 30%. This investigation was aimed to synthesis the piperine-loaded zinc oxide nanocomposite (ZnO-Pip-NC) and investigating its anticancer activity against the GC by in vitro and in vivo models by the inhibiting the apoptotic and PI3K/Akt/mTOR signaling pathways. The synthesized ZnO-Pip-NC was characterized by different techniques. The cytotoxicity of zinc oxide, piperine and the formulated ZnO-Pip-NC was tested against the AGS cells by MTT assay. The intracellular ROS level, mitochondrial membrane potential, and apoptotic cell necrosis in the AGS cells was examined by fluorescent staining techniques. The expression of apoptotic and PI3K/Akt/mTOR signaling markers were inspected by western blotting and the expression of pro0inflammatory markers analyzed by RT-PCR technique. The antioxidant levels were examined by standard methods and histopathology of gastric mucosa was analyzed. The ZnO-Pip-NC treatment appreciably inhibited the AGS cell viability. ZnO-Pip-NC treated cells also exhibited excessive intracellular ROS, diminished MMP, nuclear damages, and apoptosis induction in AGS cells. The enhanced expression of pro-apoptotic proteins and inhibition of PI3K/Akt/mTOR signaling pathway was noted in ZnO-Pip-NC treated cells. In vivo studies proved that the ZnO-Pip-NC noticeably restored the antioxidants in the GC animals and also prevented the gastric mucosa and inhibited the GC tumor formation. In conclusion, the findings of this investigation confirmed the anticancer potential of ZnO-Pip-NC against the GC via inhibiting the PI3K/Akt/mTOR signaling pathway.