Growth Inhibitory Effects Research Articles

Synthesis and Biological Evaluation of a Novel Sugar-Conjugated Platinum(II) Complex Having a Tumor-Targeting Effect.

We designed and synthesized a novel platinum complex conjugated with 2-fluorinated 2-deoxyglucoside, named FGC-Pt, to capitalize on the Warburg effect and metabolic trapping properties of [18F]2-deoxy-2-fluoro-d-glucose ([18F]FDG). Then, we conducted comprehensive in vitro and in vivo studies to evaluate the effects of FGC-Pt. In vitro cytotoxicity assays using HeLa cells revealed that FGC-Pt exhibited concentration-dependent cytotoxicity, even though its cytotoxic effect was less pronounced than that of cisplatin. In the evaluation of in vivo biodistribution in mice, platinum concentration in tumors and major organs (muscle, bone, blood, liver, and kidney) and the ratio of platinum concentration in tumors to major organs following the tail vein injection of FGC-Pt and cisplatin suggest that FGC-Pt is more retained in tumors than in other organs and tends to accumulate in tumors more than cisplatin. Furthermore, an in vivo assessment of the antitumor effect conducted in A549 cell-bearing mice demonstrated that FGC-Pt possesses substantial potential as an antitumor agent. It exhibited a tumor growth-inhibitory effect comparable to that of cisplatin while inducing lower toxicity, as evidenced by lower weight loss after administration. Herein, we successfully produced a novel compound with a tumor-growth-inhibitory effect comparable to that of cisplatin and low toxicity.

Synchronous Intravital Imaging and Cavitation Monitoring of Antivascular Focused Ultrasound in Tumor Microvasculature Using Monodisperse Low Boiling Point Nanodroplets.

Focused ultrasound-stimulated microbubbles can induce blood flow shutdown and ischemic necrosis at higher pressures in an approach termed antivascular ultrasound. Combined with conventional therapies of chemotherapy, immunotherapy, and radiation therapy, this approach has demonstrated tumor growth inhibition and profound synergistic antitumor effects. However, the lower cavitation threshold of microbubbles can potentially yield off-target damage that the polydispersity of clinical agent may further exacerbate. Here we investigate the use of a monodisperse nanodroplet formulation for achieving antivascular effects in tumors. We first develop stable low boiling point monodisperse lipid nanodroplets and examine them as an alternative agent to mediate antivascular ultrasound. With synchronous intravital imaging and ultrasound monitoring of focused ultrasound-stimulated nanodroplets in tumor microvasculature, we show that nanodroplets can trigger blood flow shutdown and do so with a sharper pressure threshold and with fewer additional events than conventionally used microbubbles. We further leverage the smaller size and prolonged pharmacokinetic profile of nanodroplets to allow for potential passive accumulation in tumor tissue prior to antivascular ultrasound, which may be a means by which to promote selective tumor targeting. We find that vascular shutdown is accompanied by inertial cavitation and complex-order sub- and ultraharmonic acoustic signatures, presenting an opportunity for effective feedback control of antivascular ultrasound.

Fluorescent bioinspired albumin/polydopamine nanoparticles and their interactions with Escherichia coli cells.

Inspired by the eumelanin aggregates in human skin, polydopamine nanoparticles (PDA NPs) are promising nanovectors for biomedical applications, especially because of their biocompatibility. We synthesized and characterized fluorescent PDA NPs of 10-25 nm diameter based on a protein containing a lysine-glutamate diad (bovine serum albumin, BSA) and determined whether they can penetrate and accumulate in bacterial cells to serve as a marker or drug nanocarrier. Three fluorescent PDA NPs were designed to allow for tracking in three different wavelength ranges by oxidizing BSA/PDA NPs (Ox-BSA/PDA NPs) or labelling with fluorescein 5-isothiocyanate (FITC-BSA/PDA NPs) or rhodamine B isothiocyanate (RhBITC-BSA/PDA NPs). FITC-BSA/PDA NPs and RhBITC-BSA/PDA NPs penetrated and accumulated in both cell wall and inner compartments of Escherichia coli (E. coli) cells. The fluorescence signals were diffuse or displayed aggregate-like patterns with both labelled NPs and free dyes. RhBITC-BSA/PDA NPs led to the most intense fluorescence in cells. Penetration and accumulation of NPs was not accompanied by a bactericidal or inhibitory effect of growth as demonstrated with the Gram-negative E. coli species and confirmed with a Gram-positive bacterial species (Staphylococcus aureus). Altogether, these results allow us to envisage the use of labelled BSA/PDA NPs to track bacteria and carry drugs in the core of bacterial cells.

A cytotoxicity and mechanistic investigation of mono- and di-chloro naphthalenes

Polychlorinated naphthalenes (PCNs) were characterized as persistent organic pollutants (POPs) that were widely distributed in the environment. Although the striking in vivo toxicity of these pollutants towards both animals and humans was well documented, their cytotoxicity and mechanism of action have not been extensively investigated. In this study, the in vitro antiproliferative activity of mono- and di-chloronaphthalenes as representative PCNs were evaluated and the results indicated strong growth inhibitory effects against mammalian cells, especially the human breast MCF-10A cell and human hepatic HL-7702 cells. 2-Chloronaphthalene with the most potent antiproliferative effects within the tested PCNs, which showed IC50 values ranging from 0.3 mM to 1.5 mM against selected human cell lines, was investigated for its working mechanisms. It promoted cellular apoptosis of MCF-10A cells upon the concentration of 200 μM. It also induced the autophagy of MCF-10A cells in a dose-dependent manner, resulting in cell death via the interaction of autophagy and apoptosis. Thus, these findings supported the theoretical foundation for interventional treatment of PCNs toxicity and also provided implications for the use of chemopreventive agents against the toxic chlorinated naphthalenes in the environments.

Hovenia dulcis Suppresses the Growth of Huh7-Derived Liver Cancer Stem Cells by Inducing Necroptosis and Apoptosis and Blocking c-MET Signaling.

Liver cancer stem cells (LCSCs) contribute to the initiation, metastasis, treatment resistance, and recurrence of hepatocellular carcinoma (HCC). Therefore, exploring potential anticancer agents targeting LCSCs may offer new therapeutic options to overcome HCC treatment failure. Hovenia dulcis Thunberg (HDT), a tree from the buckthorn family found in Asia, exhibits various biological activities, including antifatigue, antidiabetic, neuroprotective, hepatoprotective, and antitumor activities. However, the therapeutic effect of HDT in eliminating LCSCs remains to be confirmed. In this study, we evaluated the inhibitory activity of ethanol, chloroform, and ethyl acetate extracts from HDT branches on the growth of Huh7-derived LCSCs. The ethyl acetate extract of HDT (EAHDT) exhibited the most potent inhibitory activity against the growth of Huh7 LCSCs among the three HDT extracts. EAHDT suppressed the in vitro self-renewal ability of Huh7 LCSCs and reduced tumor growth in vivo using the Huh7 LCSC-transplanted chick embryo chorioallantoic membrane model. Furthermore, EAHDT not only arrested the cell cycle in the G0/G1 phase but also induced receptor-interacting protein kinase 3/mixed-lineage kinase domain-like protein-mediated necroptosis and caspase-dependent apoptosis in Huh7 LCSCs in a concentration-dependent manner. Furthermore, the growth inhibitory effect of EAHDT on Huh7 LCSCs was associated with the downregulation of c-MET-mediated downstream signaling pathways and key cancer stemness markers. Based on these findings, we propose that EAHDT can be used as a new natural drug candidate to prevent and treat HCC by eradicating LCSCs.

Dinaciclib inhibits the growth of acute myeloid leukemia cells through either cell cycle-related or ERK1/STAT3/MYC pathways

Although immature differentiation and uncontrolled proliferation of hematopoietic stem cells are thought to be the primary mechanisms of acute myeloid leukemia (AML), the pathophysiology in most cases remains unclear. Dinaciclib, a selective small molecule targeting multiple cyclin-dependent kinases (CDKs), is currently being evaluated in oncological clinical trials. Despite the proven anticancer potential of dinaciclib, the differential molecular mechanisms by which it inhibits the growth of different AML cell lines remain unclear. In the current study, we treated HL-60 and KG-1 AML cell lines with dinaciclib and investigated the potential mechanisms of dinaciclib-induced AML cell growth inhibition using flow cytometry and western blotting assays. Data from HL-60 and KG-1 AML cells were validated using human primary AML cells. The results showed that the growth inhibitory effect of dinaciclib was more sensitive in HL-60 cells (IC50: 8.46 nM) than in KG-1 cells (IC50: 14.37 nM). The protein decline in Cyclin A/B and CDK1 and cell cycle arrest in the G2/M phase were more profound in HL-60 cells, corresponding to its growth inhibition. Although the growth inhibition of KG-1 cells by dinaciclib was still pronounced, the cell cycle-associated proteins were relatively insensitive. In addition to cell cycle regulation, the activation/expression of ERK1/STAT3/MYC signaling was significantly reduced by dinaciclib in KG-1 cells compared with that in HL-60 cells. Regarding the results of primary AML cells, we observed ERK1/STAT3/MYC inhibition and cell cycle regulation in different patients. These findings suggest that the cell cycle-associated and ERK1/STAT3/MYC signaling pathways might be two distinct mechanisms by which dinaciclib inhibits AML cells, which could facilitate the development of combination therapy for AML in the future.

Disruptive Effects of Two Curcuminoids (Demethoxycurcumin and Bisdemethoxycurcumin) on the Larval Development of Drosophila melanogaster.

Juvenile hormones (JHs) play a central role in insect development, reproduction, and various physiological functions. Curcuminoids generally exhibit a wide range of biological activities, such as antioxidant, anti-inflammatory, antibacterial, and insecticidal, and they exhibit insect growth inhibitory effects. However, research on insecticidal properties of curcuminoids has been limited. Moreover, to the best of our knowledge, studies on JHs of insects and curcuminoids are lacking. Therefore, this study aimed to identify the substances that act as JH disruptors (JHDs) from edible plants. Demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC), two curcuminoids from the turmeric plant Curcuma longa L. inhibited the formation of a methoprene-tolerant (Met)-Taiman (Tai) heterodimer complex in Drosophila melanogaster, as shown through in vitro yeast two-hybrid assays. An artificial diet containing 1% (w/v) DMC or BDMC significantly reduced the number of D. melanogaster larvae in a concentration-dependent manner; larval development was disrupted, preventing the progression of larvae to pupal stages, resulting in an absence of adults. Building on the results obtained in this study on curcuminoids, researchers can use our study as a reference to develop eco-friendly pesticides.

Apoferritin-Cu(II) Nanoparticles Induce Oncosis in Multidrug-Resistant Colon Cancer Cells.

Multidrug resistance (MDR) limits the application of clinical chemotherapeutic drugs. There is an urgent need to develop non-apoptosis-inducing agents that circumvent drug resistance. Herein, four therapeutic copper complexes encapsulated in natural nanocarrier apoferritin (AFt-Cu1-4) are reported. Although they are isomers, they exhibit significantly different organelle distributions and cell death mechanisms. AFt-Cu1 and AFt-Cu3 accumulate in the cytoplasm and induce autophagy, whereas AFt-Cu2 and AFt-Cu4 can quickly enter the nucleus and trigger oncosis. Excitedly, AFt-Cu2 and AFt-Cu4 show a strong tumor growth inhibition effect in mice models bearing multidrug-resistant colon xenograft via intravenous injection. To the best of the authors' knowledge, this is the first example of metal-based nucleus-targeted oncosis inducers overcoming multidrug resistance in vivo.

P38 Mitogen-Activated Protein Kinase Inhibition of Mesenchymal Transdifferentiated Tumor Cells in Head and Neck Squamous Cell Carcinoma.

High mortality in head and neck squamous cell carcinoma (HNSCC) is due to recurrence, metastasis, and radiochemotherapy (RCT) resistance. These phenomena are related to the tumor cell subpopulation undergoing partial epithelial to mesenchymal transition (pEMT). Repeated transforming growth factor-beta (TGF-beta-1) treatment via the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway induces pEMT in SCC-25 HNSCC cells, and activates and stabilizes the pro-EMT transcription factor Slug. We investigated the growth inhibitory, cisplatin-sensitizing, and pro-apoptotic effects of p38 MAPK inhibition in cisplatin-resistant (SCC-25) and -sensitive (UPCI-SCC090) HNSCC cell lines, using two specific p38 MAPK inhibitors, SB202190 and ralimetinib. Cell viability was measured by MTT assay; cell cycle distribution and cell death were evaluated by flow cytometry; p38 MAPK phosphorylation, Slug protein stabilization, and p38 MAPK downstream targets were investigated by Western blot. p-p38 inhibitors achieved sustained phosphorylation of p38 MAPK (Thr180/Tyr182) and inhibition of its function, which resulted in decreased phosphorylation (Thr69/71) of the downstream target pATF2 in pEMT cells. Subsequently, the p-p38 inhibition resulted in reduced Slug protein levels. In accordance, p-p38 inhibition led to sensitization of pEMT cells to cisplatin-induced cell death; moreover, p-p38 inhibitor treatment cycles significantly decreased the viability of cisplatin-surviving cells. In conclusion, clinically relevant p38 inhibitors might be effective for RCT-resistant pEMT cells in HNSCC patients.

Loss of keratin 23 enhances growth inhibitory effect of melatonin in gastric cancer

Loss of keratin 23 enhances growth inhibitory effect of melatonin in gastric cancer

Fungicidal activities of chitosan-stabilized copper nanoparticles on Magnaporthe oryzae, Rhizoctonia solani, and Phytophthora capsica

Pathogenic fungi are the most common causes of economic loss in crop production. Until now, synthetic fungicides are the most effective tools for management in agriculture, but they cause a severe impact on the environment as well as several side effects for human health. The use of synthetic fungicides is prohibited in organic agriculture; however, sulfur and copper fungicides are still permitted in organic farming. In this study, chitosan-stabilized copper chitosan nanoparticles (CS-CuNPs) were synthesized and characterized via UV-Vis analysis and scanning electron microscopy (SEM). Moreover, fungicidal activities of CS-CuNPs in the range of concentrations (00, 500, and 1000 mg/L) against several plant pathogenic fungi, including Magnaporthe oryzae, Rhizoctonia solani, and Phytophthora capsici, have been assessed via filamentous fugal growth inhibition. The results indicated that the size of CS-CuNPs ranged from 70 to 74 nm with the plasmon absorption peak at 600 nm, which implied the CS-CuNPs were successfully synthesized. Furthermore, CS-CuNPs effectively inhibited the growth of all three fungi at a concentration 1000 mg/L. Among the three species, Rhizoctonia solani was the most susceptible to CS-CuNPs, with the growth inhibitory effect at 100 mg/L. In conclusion, CS-CuNPs demonstrated a strong potential for the elimination of plant pathogenic fungi and further applications in agriculture.

Intracellular Growth Inhibition and Host Immune Modulation of 3-Amino-1,2,4-triazole in Murine Brucellosis.

Catalase, an antioxidant enzyme widely produced in mammalian cells and bacteria, is crucial to mitigating oxidative stress in hostile environments. This function enhances the intracellular survivability of various intracellular growth pathogens, including Brucella (B.) abortus. In this study, to determine whether the suppression of catalase can inhibit the intracellular growth of B. abortus, we employed 3-amino-1,2,4-triazole (3-AT), a catalase inhibitor, in both RAW 264.7 macrophage cells and an ICR mouse model during Brucella infection. The intracellular growth assay indicated that 3-AT exerts growth-inhibitory effects on B. abortus within macrophages. Moreover, it contributes to the accumulation of reactive oxygen species and the formation of nitric oxide. Notably, 3-AT diminishes the activation of the nucleus transcription factor (NF-κB) and modulates the cytokine secretion within infected cells. In our mouse model, the administration of 3-AT reduced the B. abortus proliferation within the spleens and livers of infected mice. This reduction was accompanied by a diminished immune response to infection, as indicated by the lowered levels of TNF-α, IL-6, and IL-10 and altered CD4+/CD8+ T-cell ratio. These results suggest the protective and immunomodulatory effects of 3-AT treatment against Brucella infection.

10008-CBMS-1 THE NOVEL MDM4 INHIBITOR CEP-1347 ACTIVATES THE P53 PATHWAY AND BLOCKS MALIGNANT MENINGIOMA GROWTH IN VITRO AND IN VIVO

Abstract A significant proportion of meningiomas are clinically aggressive, but there is currently no effective chemotherapy for meningiomas. An increasing number of studies have been conducted to develop targeted therapies, yet none have focused on the p53 pathway as a potential target. In this study, we aimed to determine the in vitro and in vivo effects of CEP-1347, a small-molecule inhibitor of MDM4 with known safety in humans. The effects of CEP-1347 and MDM4 knockdown on the p53 pathway in human meningioma cell lines with and without p53 mutation were examined by RT-PCR and Western blot analyses. The growth inhibitory effects of CEP-1347 was examined in vitro and in a mouse xenograft model of meningioma. In vitro, CEP-1347 at clinically relevant concentrations inhibited MDM4 expression, activated the p53 pathway in malignant meningioma cells with wild-type p53, and exhibited preferential growth inhibitory effects on cells expressing wild-type p53, which was mostly mimicked by MDM4 knockdown. CEP-1347 effectively inhibited the growth of malignant meningioma xenografts at a dose that was far lower than the maximum dose that could be safely given to humans. Our findings suggest targeting the p53 pathway with CEP-1347 represents a novel and viable approach to treating aggressive meningiomas.

10014-CBMS-2 CONCURRENT TARGETING OF MDM4 AND MDM2 USING CEP-1347 AS AN EFFECTIVE THERAPEUTIC STRATEGY FOR P53 WILD-TYPE MALIGNANT BRAIN TUMORS

Abstract The development of MDM4 inhibitors as an approach to reactivating p53 in human cancer is attracting increasing attention; however, whether they affect the function of MDM2 and how they interact with MDM2 inhibitors remain unknown. We addressed this question in the present study using CEP-1347, an inhibitor of MDM4 protein expression. The effects of CEP-1347, the genetic and/or pharmacological inhibition of MDM2, and their combination on the p53 pathway in malignant brain tumor cell lines expressing wild-type p53 were investigated by RT-PCR and Western blot analyses. The growth inhibitory effects of CEP-1347 alone or in combination with MDM2 inhibition were examined by dye exclusion and/or colony formation assays. The treatment of malignant brain tumor cell lines with CEP-1347 markedly increased MDM2 protein expression, while blocking CEP-1347-induced MDM2 overexpression by genetic knockdown augmented the effects of CEP-1347 on the p53 pathway and cell growth. Blocking the MDM2-p53 interaction using the small molecule MDM2 inhibitor RG7112, but not MDM2 knockdown, reduced MDM4 expression. Consequently, RG7112 effectively cooperated with CEP-1347 to reduce MDM4 expression, activate the p53 pathway, and inhibit cell growth. The present results suggest CEP-1347-induced MDM2 overexpression combined with the selective inhibition of MDM2's interaction with p53, while preserving its ability to inhibit MDM4 expression, as a novel and rational strategy to effectively reactivate p53 in wild-type p53 cancer cells.

10168-BOT-2 ANTITUMOR AROMA THERAPY WITH LEMONGRASS ESSENTIAL OIL FOR GLIOBLASTOMA

Abstract Aromatic essential oils have been used in cancer treatment to enhance immunity, induce sedation, and reduce the side effects of chemotherapy. Recently, essential oils have been reported to have anti-tumor effects. We have been investigating anti-tumor aroma of essential oils as a novel treatment for glioblastoma and have found that hiba essential oil has a proliferation inhibitory effect. In this study, we investigated the antitumor effect of lemongrass essential oil for glioblastoma and its antitumor aromatherapy. Human glioblastoma cells (U87, T98G) and mouse brain tumor cells (RSV-M) were used. Lemongrass essential oil was added to each tumor cell line, and growth inhibition was observed in all cell lines. In addition, lemon grass essential oil showed growth inhibition effect when the tumor cells were separated from the oil, as was the case with direct administration, suggesting that the lemongrass essential oil components that evaporated acted on tumor cells in the surrounding area. The antitumor component of lemongrass essential oil was isolated and identified as citral, an antitumor factor, by gas chromatography. Analysis of the effects of citral showed that it strongly inhibited MARK4 activity and growth in three cell lines. The mechanism revealed that citral decreased the phosphorylation of Tau protein. MARK4 is highly expressed in glioblastoma and has been reported to be involved in cell proliferation. This study suggests a potential mechanism for citral to inhibit tumor cell proliferation via MARK4 in malignant gliomas. Citral is a volatile monoterpene and may exert its antitumor effect by evaporation diffusion. Lemongrass essential oil contains citral, which shows antitumor effects, and is expected to be applied to a new glioblastoma therapy using "aroma".

Production and synthesis of a novel 191Pt-labeled platinum complex and evaluation of its biodistribution in healthy mice

We previously reported that our sugar-conjugated platinum complex (cis-dichloro [(2-fluoro-α-d-glucopylanosidyl) propane-1,3-diamine] platinum: FGC-Pt) has low toxicity and tumor growth inhibitory effect comparable to that of cisplatin. We focused on radioactive Pt isotopes in order to analyze the kinetics of FGC-Pt using gamma-ray imaging techniques, assuming that FGC-Pt could be used for chemotherapy in the future. Therefore, in this study, we aimed to develop a non-invasive method to analyze the biodistribution of FGC-Pt using 191Pt-labeled FGC-Pt ([191Pt]FGC-Pt).191Pt was produced via the (n,2n) reaction induced by accelerator neutrons. [191Pt]FGC-Pt was prepared using two different methods. In the first method, [191Pt]FGC-Pt (method A) was obtained through the accelerator neutron irradiation of FGC-Pt. In the second method, [191Pt]FGC-Pt (method B) was synthesized using [191Pt]K2PtCl4, which was obtained by the accelerator neutron irradiation of K2PtCl4. Highly purified [191Pt]FGC-Pt was obtained using the latter method, which suggests that the synthetic method using a 191Pt-labeled platinum reagent is suitable for the radioactivation of platinum complexes.We also aimed to investigate whether a significant correlation existed between the biodistribution of FGC-Pt and [191Pt]FGC-Pt in healthy mice 24 h after tail vein administration. FGC-Pt and [191Pt]FGC-Pt were similarly distributed in healthy mice, with a higher accumulation in the liver and kidney 24 h post injection. In addition, a significant correlation (p < 0.05, r = 0.92) between the 191Pt radioactivity concentration (%ID/g (gamma counter)) and platinum concentration (%ID/g (ICP-MS)) was observed in 13 organs. These results suggest that 191Pt-labeled compounds, synthesized using radioactive platinum reagents, can be used to confirm the biodistribution of platinum compounds. Our study on the biodistribution of [191Pt]FGC-Pt is expected to contribute to the development of novel platinum-based drugs in the future.

Eph signal inhibition potentiates the growth-inhibitory effects of PLK1 inhibition toward cancer cells

Anti-mitotic drugs are clinically used as anti-cancer treatments. Polo-like kinase 1 (PLK1) is a promising target against cancer cell division due to its importance in the whole process of mitosis, and thus PLK1-targeting agents have been developed in the last few decades. Clinical trial studies show that several PLK1 inhibitors are generally well-tolerated. However, the response rates are limited; therefore, it is needed to improve the efficacy of those drugs. Here, we show that NVP-BHG712, an erythropoietin-producing human hepatocellular (Eph) signaling inhibitor, potentiates the growth-inhibitory effects of the PLK1 inhibitors BI2536 and BI6727 in cancer cells. This combination treatment strongly suppresses cancer spheroid formation. Moreover, the combination drastically arrests cells at mitosis by continuous activation of the spindle assembly checkpoint (SAC), thereby inducing apoptosis. SAC activation caused by the combination of NVP-BHG712 and BI2536 is due to the inhibition of centrosome maturation and separation. Although the inactivation level of the PLK1 kinase is comparable between BI2536 treatment alone and combination treatment, the combination treatment strongly inactivates MAPK signaling in mitosis. Since inhibition of MAPK signaling potentiates the efficacy of BI2536 treatment, inactivation of PLK1 kinase and MAPK signaling contributes to the strong inhibition of centrosome separation. These results suggest that Eph signal inhibition potentiates the effect of PLK1 inhibition, leading to strong mitotic arrest via SAC activation and the subsequent reduction of cancer cell survival. The combination of PLK1 inhibition and Eph signal inhibition will provide a new effective strategy for targeting cancer cell division.

Cu2O, ZnO, and Ag/ Cu2O nanoparticles synthesized by biogenic and chemical route and their effect on Pseudomonas aeruginosa and Candida albicans

Pseudomonas aeruginosa and Candida albicans are two important pathogens in public health due to the infections they cause in immunocompromised patients and with hospital stay, increasing morbimortality rates. Three groups of Cu2O, ZnO, and Ag/Cu2O nanoparticles were synthesized and characterized physicochemically and confronted to P. aeruginosa and C. albicans to determine their antibacterial effect. Statistical analyses were performed using Analysis of Variance (ANOVA) (p < 0.001). The structures of Cu2O, ZnO, and Ag/Cu2O nanoparticles were spherical, sized 6 nm, 10 nm, and 50 nm for Ag, Cu2, and Zn metals, respectively. Furthermore, a 100% antibacterial and antifungal effect against Pseudomonas aeruginosa and Candida albicans was observed for Cu2O, ZnO, and Ag/Cu2O nanoparticles respectively. It is concluded from these findings that the nanoparticles synthesized by biogenic and chemical route had a good size between 6 and 50 nm and that Cu2O, ZnO, and Ag/Cu2O nanoparticles presented an excellent antibacterial (100% growth inhibition) effect against P. aeruginosa and C. albicans (p < 0.001) compared to the control.

Polysaccharides from Spirulina platensis (PSP): promising biostimulants for the green synthesis of silver nanoparticles and their potential application in the treatment of cancer tumors

Photosynthetic cyanobacterial components are gaining great economic importance as prospective low-cost biostimulants for the green synthesis of metal nanoparticles with valuable medical and industrial applications. The current study comprises the biological synthesis of silver nanoparticles (Ag-NPs) using soluble polysaccharides isolated from Spirulina platensis (PSP) as reducing and capping agents. FTIR spectra showed major functional groups of PSP and biogenic silver nanoparticles including O–H, C–H (CH2), C–H (CH3), C=O, amide, and COO– groups. The UV/Vis spectroscopy scan analyses of the extracted PSP showed absorption spectra in the range of 200–400 nm, whereas the biogenic Ag-NPs showed a maximum spectrum at 285 nm. Transmission electron microscopy (TEM) analysis of the synthesized Ag-NPs showed spherical nanoparticles with mean size between 12 and 15.3 nm. The extracted PSP and Ag-NPs exhibited effective cytotoxic activity against Hep-G2 (human hepatocellular carcinoma). The IC50 for PSP and Ag-NPs were 65.4 and 24.5 µg/mL, respectively. Moreover, cell apoptosis assays for PSP and Ag-NPs against the growth of Hep-G2 cells revealed superior growth inhibitory effects of the green synthesized Ag-NPs that encouraged tracing the apoptotic signalling pathway. In conclusion, the current study demonstrated an unprecedented approach for the green synthesis of silver nanoparticles (NPs), using the polysaccharide of Spirulina platensis as reducing and capping agents, with superior anticancer activity against a hepatocellular carcinoma cell line.

In vitro activity of various Kenyan tea extracts against HeLa human cervical cancer cell line and molecular docking of tea catechins on high-risk HPV16E6 protein

Tea (Camellia sinensis) has been revealed to possess potential anticancer properties attributed to its catechin content. This study aimed to investigate the growth-inhibitory effects of various tea extracts on the HeLa cell line and molecular docking analysis of catechins on Human papillomavirus16 oncoprotein 6 (HPV16E6). Different catechins content in black, green, and purple tea were determined by using High-performance liquid chromatography (HPLC); molecular docking of four main catechins on HPV16E6 and in vitro antiproliferative activity and cell apoptosis assay were carried out. Molecular docking results suggested that the tea catechins have the potential to bind to the HPV16 E6 oncoprotein involved in cervical cancer development. The antiproliferative assay results indicated that purple tea had the highest inhibitory activity at both 24 h and 48 h, with IC50 values of 121.1 ± 3.25 μg/mL and 100.1 ± 3.76 μg/mL respectively, followed by green tea with 168.9 ± 12.59 μg/mL and 124.7 ± 3.53 μg/mL IC50 while black tea showed the least effectiveness with IC50 of 221 ± 19.35 μg/mL and 159.6 ± 2.33 μg/mL. DNA fragmentation, a characteristic of apoptosis, was observed in cells treated with the tea extracts. All three tea extracts demonstrated potential anti-cervical cancer activity bIy inhibiting cell proliferation and inducing apoptosis. The tea catechins showed promising interactions with the HPV16 E6 oncoprotein.