Antitumor Efficacy of Arylquin 1 through Dose-Dependent Cytotoxicity, Apoptosis Induction, and Synergy with Radiotherapy in Glioblastoma Models.

Glioblastoma (GBM), the most aggressive form of brain cancer, is characterized by rapid growth and resistance to conventional therapies. Current treatments offer limited effectiveness, leading to poor survival rates and the need for novel therapeutic strategies. Arylquin 1 has emerged as a potential therapeutic candidate because of its unique mechanism of inducing apoptosis in cancer cells without affecting normal cells. This study investigated the efficacy of Arylquin 1 against GBM using the GBM8401 and A172 cells by assessing its dose-dependent cytotoxicity, apoptosis induction, and synergy with radiotherapy. In vitro assays demonstrated a significant reduction in cell viability and increased apoptosis, particularly at high concentrations of Arylquin 1. Migration and invasion analyses revealed notable inhibition of cellular motility. In vivo experiments on NU/NU nude mice with intracranially implanted GBM cells revealed that Arylquin 1 substantially reduced tumor growth, an effect magnified by concurrent radiotherapy. These findings indicate that by promoting apoptosis and enhancing radiosensitivity, Arylquin 1 is a potent therapeutic option for GBM treatment.

Small molecules baicalein and cinnamaldehyde are potentiators of measles virus-induced breast cancer oncolysis.

BACKGROUND: Although the breast cancer mortality has slowed down from 2008 to 2017, breast cancer incidence rate continues to rise and thus, new and/or improved treatments are highly needed. Among them, oncolytic virotherapy which has the ability of facilitating the antitumor adaptive immunity, appears as a promising anticancer therapy. Oncolytic measles virus (MV) is particularly suitable for targeting breast cancer due to the upregulation of MV's receptor nectin-4. Nonetheless, with limited clinical success currently, ways of boosting MV-induced breast cancer oncolysis are therefore necessary. Oncolytic virotherapy alone and combined with chemotherapeutic drugs are two strategic areas with intensive development for the search of anticancer drugs. Considering that baicalein (BAI) and cinnamaldehyde (CIN) have demonstrated antitumor properties against multiple cancers including breast cancer, they could be good partners for MV-based oncolytic virotherapy. PURPOSE: To assess the in vitro effect of BAI and CIN with MV and assess their combination effects. METHODS: We examined the combinatorial cytotoxic effect of oncolytic MV and BAI or CIN on MCF-7 breast cancer cells. Potential anti-MV activities of the phytochemicals were first investigated in vitro to determine the optimal combination model. Synergism of MV and BAI or CIN was then evaluated in vitro by calculating the combination indices. Finally, cell cycle analysis and apoptosis assays were performed to confirm the mechanism of synergism. RESULTS: Overall, the viral sensitization combination modality using oncolytic MV to first infect MCF-7 breast cancer cells followed by drug treatment with BAI or CIN was found to produce significantly enhanced tumor killing. Further mechanistic studies showed that the combinations 'MV-BAI' and 'MV-CIN' display synergistic anti-breast cancer effect, mediated by elevated apoptosis. CONCLUSION: We demonstrated, for the first time, effective combination of oncolytic MV with BAI or CIN that could be further explored and potentially developed into novel therapeutic strategies targeting nectin-4-marked breast cancer cells.

Ursolic Acid and Its Nanoparticles Are Potentiators of Oncolytic Measles Virotherapy against Breast Cancer Cells.

Oncolytic viruses (OVs) and phytochemical ursolic acid (UA) are two efficacious therapeutic candidates in development against breast cancer, the deadliest women's cancer worldwide. However, as single agents, OVs and UA have limited clinical efficacies. As a common strategy of enhancing monotherapeutic anticancer efficacy, we explored the combinatorial chemovirotherapeutic approach of combining oncolytic measles virus (MV), which targets the breast tumor marker Nectin-4, and the anticancer UA against breast adenocarcinoma. Our findings revealed that in vitro co-treatment with UA synergistically potentiated the killing of human breast cancer cells by oncolytic MV, without UA interfering the various steps of the viral infection. Mechanistic studies revealed that the synergistic outcome from the combined treatment was mediated through UA's potentiation of apoptotic killing by MV. To circumvent UA's poor solubility and bioavailability and strengthen its clinical applicability, we further developed UA nanoparticles (UA-NP) by nanoemulsification. Compared to the non-formulated UA, UA-NP exhibited improved drug dissolution property and similarly synergized with oncolytic MV in inducing apoptotic breast cancer cell death. This oncolytic potentiation was partly attributed to the enhanced autophagic flux induced by the UA-NP and MV combined treatment. Finally, the synergistic effect from the UA-NP and MV combination was also observed in BT-474 and MDA-MB-468 breast cancer cells. Our study thus highlights the potential value of oncolytic MV and UA-based chemovirotherapy for further development as a treatment strategy against breast cancer, and the feasibility of employing nanoformulation to enhance UA's applicability.

Chemovirotherapeutic Treatment Using Camptothecin Enhances Oncolytic Measles Virus-Mediated Killing of Breast Cancer Cells.

Oncolytic virotherapy represents an emerging development in anticancer therapy. Although it has been tested against a variety of cancers, including breast cancer, the efficacy of oncolytic viral vectors delivered as a monotherapy is limited. Enhancing viral oncolytic therapies through combination treatment with anticancer agents is a feasible strategy. In this study, we considered a chemovirotherapeutic approach for treating breast adenocarcinoma using oncolytic measles virus (MV) and the chemotherapeutic agent camptothecin (CPT). Our results demonstrated that co-treatment of MV with CPT yielded enhanced cytotoxicity against breast cancer cells. Low dosage CPT combined with MV was also found to elicit the same therapeutic effect as high doses of CPT. At the lower dosage used, CPT did not inhibit the early stages of MV entry, nor reduce viral replication. Further studies revealed that co-treatment induced significantly enhanced apoptosis of the breast cancer cells compared to either MV or CPT alone. Overall, our findings demonstrate the potential value of MV plus CPT as a novel chemovirotherapeutic treatment against breast cancer and as a strategy to enhance MV oncolytic activity.

Rapid sonochemical synthesis of MCM-41 type benzene-bridged periodic mesoporous organosilicas.

Benzene-bridged periodic mesoporous organosilicas (PMOs) with the MCM-41 were synthesized by a rapid sonochemical process via co-condensation of tetraethoxysilane (TEOS) and 1,4-bis(triethoxysilyl) benzene (BTEB) under basic conditions within a few minutes using cetyltrimethylammoniumbromide (CTMABr) as a structure-directing agent. The molar ratio of the silicon precursors and the synthesis time were varied in order to investigate their influence on the structural ordering of the materials. The characteristics of the materials were evaluated by X-ray diffraction (XRD), N2-sorption, transmission electron microscopy (TEM) and solid-state NMR spectroscopy. The resultant materials exhibited well-ordered hexagonal mesostructures with surface areas in the range of 602-1237 m(2)/g, pore volumes of 0.37-0.68 cm(3)/g, and pore diameters in the range of 2.5-3.5 nm. Two dimensional (29)Si{(1)H} heteronuclear correlation (HETCOR) NMR spectra confirmed the formation of a single mesophase with various Q (from TEOS) and T (from BTEB) silicon species located randomly within the pore walls due to the co-condensation of BTEB and TEOS, which excluded the possibility of formation of island or two separate phases within such a short synthesis time. The prime advantage of the present synthesis route is that it can effectively reduce the total synthesis time from days to a few minutes, much shorter than the conventional benzene-bridged PMOs synthesis methods.

Synthesis, Multinuclear NMR Characterization and Dynamic Property of Organic-Inorganic Hybrid Electrolyte Membrane Based on Alkoxysilane and Poly(oxyalkylene) Diamine.

Organic-inorganic hybrid electrolyte membranes based on poly(propylene glycol)-block-poly(ethylene glycol)-block-poly(propylene glycol) bis(2-aminopropyl ether) complexed with LiClO4 via the co-condensation of tetraethoxysilane (TEOS) and 3-(triethoxysilyl)propyl isocyanate have been prepared and characterized. A variety of techniques such as differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, alternating current (AC) impedance and solid-state nuclear magnetic resonance (NMR) spectroscopy are performed to elucidate the relationship between the structural and dynamic properties of the hybrid electrolyte and the ion mobility. A VTF (Vogel-Tamman-Fulcher)-like temperature dependence of ionic conductivity is observed for all the compositions studied, implying that the diffusion of charge carriers is assisted by the segmental motions of the polymer chains. A maximum ionic conductivity value of 5.3 × 10-5 Scm-1 is obtained at 30 °C. Solid-state NMR results provide a microscopic view of the effects of salt concentrations on the dynamic behavior of the polymer chains.

Synthesis and solid-state NMR characterization of cubic mesoporous silica SBA-1 functionalized with sulfonic acid groups.

Well-ordered cubic mesoporous silicas SBA-1 functionalized with sulfonic acid groups have been synthesized through in situ oxidation of mercaptopropyl groups with H(2)O(2) via co-condensation of tetraethoxysilane (TEOS) and 3-mercaptopropyltrimethoxysilane (MPTMS) templated by cetyltriethylammonium bromide (CTEABr) under strong acidic conditions. Various synthesis parameters such as the amounts of H(2)O(2) and MPTMS on the structural ordering of the resultant materials were systematically investigated. The materials thus obtained were characterized by a variety of techniques including powder X-ray diffraction (XRD), multinuclear solid-state Nuclear Magnetic Resonance (NMR) spectroscopy, (29)Si{(1)H} 2D HETCOR (heteronuclear correlation) NMR spectroscopy, thermogravimetric analysis (TGA), and nitrogen sorption measurements. By using (13)C CPMAS NMR technique, the status of the incorporated thiol groups and their transformation to sulfonic acid groups can be monitored and, as an extension, to define the optimum conditions to be used for the oxidation reaction to be quantitative. In particular, (29)Si{(1)H} 2D HETCOR NMR revealed that the protons in sulfonic acid groups are in close proximity to the silanol Q(3) species, but not close enough to form a hydrogen bond.

A simple one-pot route to mesoporous silicas SBA-15 functionalized with exceptionally high loadings of pendant carboxylic acid groups.

Ordered SBA-15 functionalized with a high loading of pendant carboxylate groups has been synthesized via co-condensation of tetraethoxysilane (TEOS) and carboxyethylsilanetriol sodium salt (CES) templated by Pluronic P123 under acidic conditions.