Dendritic cell (DC)-based cancer immunotherapies have been studied extensively. In cancer immunotherapy, the initial key step is the delivery of tumor-specific antigens, leading to the maturation and activation of DCs. To promote effective antigen delivery, liposome-based delivery systems for tumor-specific antigens have been investigated, and although promising, a triggered release of the antigen from the liposome is required to attain an optimum immune response. In this study, we developed CO2-bubble-generating thermosensitive liposomes (BG-TSLs) that encapsulate whole tumor cell lysates (TCLs). The release of the lysate from BG-TSLs can be triggered using near-infrared (NIR) irradiation. We also developed BG-TSLs able to encapsulate doxorubicin (DOX) for combination therapy. The DOX-BG-TSLs and TCL-BG-TSLs have a mean particle size of 114.17 ± 8.28 nm and 123.8 ± 10.2 nm and a surface charge of -22.56 ± 1.3 mV and -28.9 ± 0.8 mV, respectively. CO2 bubble generation within TCL-BG-TSLs and DOX-BG-TSLs by NIR irradiation led to the burst release of TCL or DOX. TCL release from TCL-BG-TSLs promoted dendritic cell maturation and activation, leading to the emergence of antigen-specific cytotoxic CD8+ T cells. The combination of TCL-BG-TSLs with DOX-BG-TSLs showed a significantly greater antitumor efficacy in B16F10 tumor-bearing mice compared to that seen in the control mice (P < 0.001). Taken together, our liposomal delivery system, combined with NIR irradiation, could enhance the therapeutic efficacy of cancer immunotherapies.
6'-O-galloylpaeoniflorin (GPF) is a galloylated derivate of paeoniflorin and a key chemical constituent of the peony root, a perennial flowering plant that is widely used as an herbal medicine in East Asia. This study is the first investigation of the cytoprotective effects of GPF against hydrogen peroxide (H2O2)-induced cell injury and death in human HaCaT keratinocytes. GPF demonstrated a significant scavenging capacity against the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical, H2O2-generated intracellular reactive oxygen species (ROS), the superoxide anion radical (O2 (-)), and the hydroxyl radical (•OH). GPF also safeguarded HaCaT keratinocytes against H2O2-provoked apoptotic cell death and attenuated oxidative macromolecular damage to DNA, lipids, and proteins. The compound exerted its cytoprotective actions in keratinocytes at least in part by decreasing the number of DNA strand breaks, the levels of 8-isoprostane (a stable end-product of lipid peroxidation), and the formation of carbonylated protein species. Taken together, these results indicate that GPF may be developed as a cytoprotector against ROS-mediated oxidative stress.
In this study, we investigated the molecular mechanisms underlying the anti-proliferative effects of Compound K, with specific reference to histone modification. Exposure of HT-29 human colon cancer cells to Compound K resulted in time-dependent inhibition of histone deacetylase (HDAC) activity, mRNA and protein expression. Compound K treatment induced unmethylation of the RUNX3 promoter region such as TSA treatment and an accumulation of acetylated histones H3 and H4 within the total cellular chromatin, resulting in an enhanced ability of these histones to bind to the promoter sequences of the tumor suppressor gene Runt-related transcription factor 3 (RUNX3). Treatment of cells with Compound K increased the mRNA and protein expression of RUNX3, as well as p21, a downstream target of RUNX3. These alterations were consistent with cell cycle arrest at the G0/G1 phases and induction of apoptosis. Our results provide new insights into the mechanisms of Compound K action in human colorectal cancer cells and suggest that HDAC inhibition presents a novel approach to prevent or treat colorectal cancer.
We investigated the protective effects of chlorogenic acid (CGA), a polyphenol compound, on oxidative damage induced by UVB exposure on human HaCaT cells.In a cell-free system, CGA scavenged 1,1-diphenyl-2-picrylhydrazyl radicals, superoxide anions, hydroxyl radicals, and intracellular reactive oxygen species (ROS) generated by hydrogen peroxide and ultraviolet B (UVB).Furthermore, CGA absorbed electromagnetic radiation in the UVB range (280-320 nm).UVB exposure resulted in damage to cellular DNA, as demonstrated in a comet assay; pre-treatment of cells with CGA prior to UVB irradiation prevented DNA damage and increased cell viability.Furthermore, CGA pre-treatment prevented or ameliorated apoptosis-related changes in UVB-exposed cells, including the formation of apoptotic bodies, disruption of mitochondrial membrane potential, and alterations in the levels of the apoptosis-related proteins Bcl-2, Bax, and caspase-3.Our findings suggest that CGA protects cells from oxidative stress induced by UVB radiation.
Context: Our previous work demonstrated that an ethyl acetate extract derived from Sargassum muticum (Yendo) Fenshol (SME) protected human HaCaT keratinocytes against ultraviolet B (UVB)-induced oxidative stress by increasing antioxidant activity in the cells, thereby inhibiting apoptosis.Objective: The aim of the current study was to further elucidate the anti-apoptotic mechanism of SME against UVB-induced cell damage.Materials and methods: The expression levels of several apoptotic-associated and mitogen-activated kinase (MAPK) signaling proteins were determined by western blot analysis of UVB-irradiated HaCaT cells with or without prior SME treatment. In addition, the loss of mitochondrial membrane potential (Δψm) was detected using flow cytometry or confocal microscopy and the mitochondria membrane-permeate dye, JC-1. Apoptosis was assessed by quantifying DNA fragmentation and apoptotic body formation. Furthermore, cell viability was evaluated using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay.Results: SME absorbed electromagnetic radiation in the UVB range (280–320 nm) of the UV/visible light spectrum. SME also increased Bcl-2 and Mcl-1 expression in UVB-irradiated cells and decreased the Bax expression. Moreover, SME inhibited the UVB-induced disruption of mitochondrial membrane potential and prevented UVB-mediated increases in activated caspase-9 and caspase-3 (an apoptotic initiator and executor, respectively) levels. Notably, treatment with a pan-caspase inhibitor enhanced the anti-apoptotic effects of SME in UVB-irradiated cells. Finally, SME reduced the UVB-mediated phosphorylation of p38 MAPK and JNK, and prevented the UVB-mediated dephosphorylation of Erk1/2 and Akt.Discussion and conclusion: The present results indicate that SME safeguards HaCaT keratinocytes from UVB-mediated apoptosis by inhibiting a caspase-dependent signaling pathway.
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