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Background: Linalool is a monoterpene compound with various potential therapeutic applications in several medical fields. Previous studies have indicated the activity of linalool against cell lines; however, its high level of toxicity restricts its use. The aim of this study was to design and manufacture compounds with a novel structure that can be used for loading linalool, to reduce its toxicity and improve its reachable ability., Methods: We synthesized and characterized a new molecule for loading linalool onto gold nanoparticles (GNPs) capped with glutathione and conjugated with a CALNN peptide. Linalool was loaded onto the GNPs via the reaction of the surface groups of both linalool and the GNPs. Moreover, the target peptide could be loaded onto the surface of the GNPs via a chemical reaction. The cytotoxic effects of linalool-GNP (LG) and linalool-GNP-CALNN peptide (LGC) conjugates against ovarian cancer cells were investigated, as were the possible mechanisms underlying the induction of apoptosis., Results: Our findings illustrated the significant antiproliferative effect of LG and LGC on SKOV-3 cells. The cytotoxicity assay demonstrated that LG and LGC were selectively toxic in cancer cells and induced apoptosis by activating caspase-8, the p53 protein, and various proteins involved in apoptosis. The present data demonstrated that LG and LGC have a high therapeutic potential and should be given particular consideration as anticancer drug-delivery systems, as LG and LGC were remarkably more cytotoxic against a cancer cell line than were linalool and GNPs alone., Conclusion: We concluded that LG and LGC are promising compounds that can be used for treating ovarian cancer (SKOV-3) cells via the induction of apoptosis through extrinsic and intrinsic pathways., Competing Interests: All authors report no conflicts of interest in this work., (© 2020 Jabir et al.)

In the current study, the surface of superparamagnetic iron oxide (SPION) was coated with dextran (DEX), and conjugated with folic acid (FA), to enhance the targeted delivery and uptake of vinblastine (VBL) in PANC-1 pancreatic cancer cells. Numerous analyses were performed to validate the prepared FA-DEX-VBL-SPION, such as field emission scanning transmission electron microscopy, high-resolution transmission electron microscopy, dynamic light scattering (DLS), Zeta Potential, Fourier transform infrared spectroscopy, and vibrating sample magnetometry (VSM). The delivery system capacity was evaluated by loading and release experiments. Moreover, in vitro biological studies, including a cytotoxicity study, cellular uptake assessment, apoptosis analysis, and real-time PCR, were carried out. The results revealed that the obtained nanocarrier was spherical with a suitable dispersion and without visible aggregation. Its average size, polydispersity, and zeta were 74 ± 13 nm, 0.080, and -45 mV, respectively. This dual functional nanocarrier also exhibited low cytotoxicity and a high apoptosis induction potential for successful VBL co-delivery. Real-time quantitative PCR analysis demonstrated the activation of caspase-3 , NF-1 , PDL-1 , and H-ras inhibition, in PANC-1 cells treated with the FA-VBL-DEX-SPION nanostructure. Close inspection of the obtained data proved that the FA-VBL-DEX-SPION nanostructure possesses a noteworthy chemo-preventive effect on pancreatic cancer cells through the inhibition of cell proliferation and induction of apoptosis.

Hybrid nanomaterials with unique physiochemical properties have received a lot of attention, making them attractive for application in different fields like cancer treatment. This study was designed to investigate the combined effects of single-walled carbon nanotubes (SWCNTs) hybridized with silver titanium dioxide composite (SWCNTs@Ag–TiO2). Transmission electron microscopy and field emission scanning electron microscopy images demonstrated the accumulation of SWCNTs with Ag–TiO2 due to an increased main grain size with functionalization to 40 nm. The D and G bands in SWCNTs @Ag–TiO2 shifted to 1,366 and 1,534 cm−1, respectively. SWCNTs@Ag-TiO2 were assessed for their cytotoxicity and autophagy induction in liver cancer cells (Hep-G2) using the lactate dehydrogenase assay, MTT assay, and flow cytometry methods. The results showed that SWCNTs and SWCNTs@Ag–TiO2 exhibited strong anti-cancer activity in vitro against Hep-G2 cells by inducing apoptosis and autophagy in liver cancer cells via controlling the AKT and JNK mitogen-activated protein kinase pathways. The results show that SWCNTs and SWCNTs coated with silver/titanium dioxide (SWCNTs@Ag–TiO2) reduce the cells’ viability and proliferation. It was shown that an excessive amount of reactive oxygen species was a crucial mediator of both the cell death caused by SWCNTs and the cell death caused by SWCNTs combined with Ag–TiO2. Based on these findings, it appears that SWCNTs and SWCNTs@Ag–TiO2 have the potential to be developed as nanotherapeutics for the treatment of liver cancer cells.

Gold nanoparticles (GNPs) tagged with peptides are pioneers in bioengineered cancer therapy. The aim of the current work was to elucidate the potential anticancer interactions between doxorubicin and GNPs loaded with tumor necrosis factor-alpha (TNF-α). To investigate whether GNPs loaded with TNF and doxorubicin could stimulate autophagy and apoptosis in breast cancer cells. Two human breast cancer cell lines, MCF-7 and AMJ-13, as well as different apoptotic and autophagy markers, were used. In both cell types, treatment with TNF-loaded GNPs in conjunction with doxorubicin increased the production of apoptotic proteins including Bad, caspase-3, caspase-7, and p53 with upregulation of the LC3-II and Beclin1 proteins. In addition, the findings showed that the mitogen-activated protein kinase signaling pathway was dramatically affected by the GNPs loaded with TNF-α and combined with doxorubicin. This had the effect of decreasing p-AKT while simultaneously increasing p-JNK1/2. The findings demonstrated that GNPs loaded with TNF-α and combined with doxorubicin can induce both autophagy and apoptosis in breast cancer cells. These results suggest that TNF- and doxorubicin-loaded GNPs provide a therapeutic option as a nanomedicine to inhibit the proliferation of breast cancer.

Aim: The cytotoxic effects of graphene oxide nanoparticles (GONPs) using MTT assays, observance of apoptotic markers, and oxidative stress were outlined. Materials & methods: Rat embryonic fibroblasts (REFs) and human epithelial breast cells (HBLs) were used at 250, 500 and 750 μg/ml concentrations. Results: Significant cytotoxic and apoptotic effects were observed. Analyses of CYP2E1 and malondialdehyde concentrations in REF and HBL-100 cell lines after exposing to GONPs confirmed the nanomaterials toxicity. However, the glutathione levels in REF and HBL-100 cell lines showed a substantial reduction compared with the control. The cytochrome CYP2E1, glutathione, malondialdehyde and caspase-3 alterations provided a plausible interlinked relationship. Conclusion: The study confirmed the GONPs cytotoxic effects on REF and HBL-100 cell lines. The outcome suggested caution in wide-spread applications of GONPs, which could have implications for occupational health also. [ABSTRACT FROM AUTHOR]

Seagrass is a natural, renewable, and much unexplored marine resource, which are capable, and reliable sources in the field of pharmaceuticals and drug discovery. The seagrass, Syringodium isoetifolium is our target plant for the study, which was collected from the Ramanathapuram district, Tamil Nadu. The current study is focused to evaluate the cytotoxic, cell cycle arrest, and apoptotic induction activities of the hydroalcoholic extract of S. isoetifolium against the human breast cancer (MCF-7) cell line. The cytotoxic evaluation revealed that the extract inhibited MCF-7 proliferation with IC 50 value of 230.32 μg/ml. Evaluation of MCF-7 cell cycles demonstrated that the extract arrested the cell cycle in the S phase and continued to the G2/M phase at half of the IC 50 value. The extract induced apoptotic of MCF-7 cells about 30.61% which was nearly the same with aripiprazole as a positive control (52.35%). Nootkatone significantly binds to the target proteins – HSP 90 and HER2 kinase with the least binding energy was predicted as the most active anticancer compounds by a molecular docking study. In light of the findings, it can be said that the hydroalcoholic extract of S. isoetifolium has the potential to be a therapeutic agent for breast malignancies by acting as an anticancer component. It can be used as an anticancer agent on its own and/or as a scaffold for analog synthesis to develop novel anticancer agents with improved therapeutic efficacy. [ABSTRACT FROM AUTHOR]

In this study, a platinum(II) complex ([Pt(H2L)(PPh3)] complex) containing a thiocarbohydrazone as the ligand was tested as an anti-proliferative agent against ovarian adenocarcinoma (Caov-3) and human colorectal adenocarcinoma (HT-29) through MTT assays. Apoptotic markers were tested by the AO/PI double staining assay and DNA fragmentation test. Flow cytometry was conducted to measure cell cycle distribution, while the p53 and caspase-8 pathways were tested via immunofluorescence assay. Results demonstrated that the cytotoxic effect of the Pt(II)-thiocarbohydrazone complexes against Caov-3 and HT-29 cells was highly significant, and this effect triggered the activation of the p53 and caspase-8 pathways. Besides, apoptosis stimulated by the Pt(II)-thiocarbohydrazone complex was associated with cell cycle arrest at the G0/G1 phase. These findings suggest that the target complex inhibited the proliferation of Caov-3 and HT-29 cells, resulting in the arrest of the cell cycle and induction of apoptosis via the stimulation of the p53 and caspase-8 pathways. The present data suggests that the Pt(II)-thiocarbohydrazone complex could also be a promising chemotherapeutic agent for other types of cancer cells. [ABSTRACT FROM AUTHOR]

Background: Advanced nanobiotechnology provides safe and efficient drug delivery systems to deliver chemotherapy that targets cancer cells efficiently. Methods: A polymeric-magnetic nanocarrier was composed of a dextran (DEX) shell, a superparamagnetic iron oxide (SPION) core and was conjugated with folate (FA) to carry the anticancer drug vincristine (VNC) in Tera-1 testicular tumor cells. The molecular mechanisms by which apoptosis was induced were analyzed using flow cytometry and qPCR, which exhibited anticancer activity of nanoparticles (NPs). Results: This nanocarrier revealed a controlled release of VNC in citrate and phosphate buffer solutions that were maintained at pH 5.5 and pH 7.4, respectively. The Inhibitory concentration (IC50) values were greater than 5 mg/mL and displayed ten times higher cytotoxicity than the comparable free drug concentration. The Caspase-9 and P53 expressions were increased, whereas P21 and AKt1 decreased noticeably in the treated cells. The results point to the possible activation of apoptosis following treatment with NPs loaded with vincristine. [ABSTRACT FROM AUTHOR]

Background: Super-paramagnetic iron oxide nanoparticles (SPION) contain a chemotherapeutic drug and are regarded as a promising technique for improving targeted delivery into cancer cells. Results: In this study, the fabrication of 5-fluorouracil (5-FU) was investigated with loaded Dextran (DEXSPION) using the co-precipitation technique and conjugated by folate (FA). These nanoparticles (NPs) were employed as carriers and anticancer compounds against liver cancer cells in vitro. Structural, magnetic, morphological characterization, size, and drug loading activities of the obtained FA-DEX-5-FUSPION NPs were checked using FTIR, VSM, FESEM, TEM, DLS, and zeta potential techniques. The cellular toxicity effect of FA-DEX-5-FU-SPION NPs was evaluated using the MTT test on liver cancer (SNU-423) and healthy cells (LO2). Furthermore, the apoptosis measurement and the expression levels of NF-1, Her-2/neu, c-Raf-1, and Wnt-1 genes were evaluated post-treatment using flow cytometry and RT-PCR, respectively. The obtained NPs were spherical with a suitable dispersity without noticeable aggregation. The size of the NPs, polydispersity, and zeta were 74 ± 13 nm, 0.080 and -45 mV, respectively. The results of the encapsulation efficiency of the nano-compound showed highly colloidal stability and proper drug maintenance. The results indicated that FA-DEX-5-FU-SPION demonstrated a sustained release profile of 5-FU in both phosphate and citrate buffer solutions separately, with higher cytotoxicity against SNU-423 cells than against other cells types. These findings suggest that FA-DEX-SPION NPs exert synergistic effects for targeting intracellular delivery of 5-FU, apoptosis induction, and gene expression stimulation. Conclusions: The findings proved that FA-DEX-5-FU-SPION presented remarkable antitumor properties; no adverse subsequences were revealed against normal cells. [ABSTRACT FROM AUTHOR]