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Oxidative stress enhances cellular DNA oxidation and may cause mutations in DNA bases, including 8‑oxoguanine (8‑oxoG). Our recent study reported that exposure of cells to non‑thermal dielectric barrier discharge (DBD) plasma generates reactive oxygen species and damages DNA. The present study investigated the effect of non‑thermal DBD plasma exposure on the formation of 8‑oxoG in HaCaT human keratinocytes. Cells exposed to DBD plasma exhibited increased level of 8‑oxoG. In addition, mRNA and protein expression levels of 8‑oxoguanine glycosylase 1 (OGG1), an 8‑oxoG repair enzyme, were reduced in plasma‑exposed cells. Furthermore, the expression level of nuclear factor erythroid 2‑related factor 2 (Nrf2), a transcription factor that regulates OGG1 gene expression, was reduced following exposure to DBD plasma. Pretreatment of cells with an antioxidant, N‑acetyl cysteine (NAC), prior to plasma exposure suppressed the formation of 8‑oxoG and restored the expression levels of OGG1 and Nrf2. In addition, phosphorylation of protein kinase B (Akt), which regulates the activation of Nrf2, was reduced following plasma exposure. However, phosphorylation was restored by pretreatment with NAC. These findings suggested that non‑thermal DBD plasma exposure generates 8‑oxoG via inhibition of the Akt‑Nrf2‑OGG1 signaling pathway in HaCaT cells.

Skin aging is the most readily observable process involved in human aging. Ultraviolet B (UVB) radiation causes photo-oxidation via generation of reactive oxygen species (ROS), thereby damaging the nucleus and cytoplasm of skin cells and ultimately leading to cell death. Recent studies have shown that high levels of solar UVB irradiation induce the synthesis of matrix metalloproteinases (MMPs) in skin fibroblasts, causing photo-aging and tumor progression. The MMP family is involved in the breakdown of extracellular matrix in normal physiological processes such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes such as arthritis and metastasis. We investigated the effect of diphlorethohydroxycarmalol (DPHC) against damage induced by UVB radiation in human skin keratinocytes. In UVB-irradiated cells, DPHC significantly reduced expression of MMP mRNA and protein, as well as activation of MMPs. Furthermore, DPHC reduced phosphorylation of ERK and JNK, which act upstream of c-Fos and c-Jun, respectively; consequently, DPHC inhibited the expression of c-Fos and c-Jun, which are key components of activator protein-1 (AP-1, up-regulator of MMPs). Additionally, DPHC abolished the DNA-binding activity of AP-1, and thereby prevented AP-1-mediated transcriptional activation. These data demonstrate that by inactivating ERK and JNK, DPHC inhibits induction of MMPs triggered by UVB radiation.

In this study, we evaluated the hypothesis that a marine brown algae, Dictyopteris undulata ethanol extract (DUE), provokes apoptosis in a human melanoma cell line, A2058, via reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress. DUE inhibited A2058 cell proliferation and increased apoptotic body formation, as indicated by the presence of fragmented nuclei and the activation of caspase-3. Moreover, DUE-treated cells showed elevated ER staining, mitochondrial calcium cation (Ca2+) overloading, augmented levels of ER stress-related and cell death modulatory proteins, including RNA-dependent protein kinase-related ER kinase, phospho-inositol-requiring enzyme 1α, phospho-eukaryotic translation initiation factor 2α, and CCAAT/enhancer-binding protein-homologous protein, as well as increased intracellular ROS levels. However, the antioxidant N-acetyl cysteine reversed the elevated ROS levels, decreased apoptosis, and mitigated ER stress in A2058 cells following DUE treatment. These findings suggest that DUE treatment triggers apoptosis in human melanoma cells through a mechanism involving ER stress and ROS.

Fucodiphlorethol G (6'-[2,4-dihydroxy-6-(2,4,6-trihydroxyphenoxy)phenoxy]biphenyl-2,2',4,4',6-pentol) is a compound purified from Ecklonia cava, a brown alga that is widely distributed offshore of Jeju Island. This study investigated the protective effects of fucodiphlorethol G against oxidative damage-mediated apoptosis induced by ultraviolet B (UVB) irradiation. Fucodiphlorethol G attenuated the generation of 2, 2-diphenyl-1-picrylhydrazyl radicals and intracellular reactive oxygen species in response to UVB irradiation. Fucodiphlorethol G suppressed the inhibition of human keratinocyte growth by UVB irradiation. Additionally, the wavelength of light absorbed by fucodiphlorethol G was close to the UVB spectrum. Fucodiphlorethol G reduced UVB radiation-induced 8-isoprostane generation and DNA fragmentation in human keratinocytes. Moreover, fucodiphlorethol G reduced UVB radiation-induced loss of mitochondrial membrane potential, generation of apoptotic cells, and active caspase-9 expression. Taken together, fucodiphlorethol G protected human keratinocytes against UVB radiation-induced cell damage and apoptosis by absorbing UVB radiation and scavenging reactive oxygen species.

Colorectal cancer is a common type of tumor among both men and women worldwide. Conventional remedies such as chemotherapies pose the risk of side‑effects, and in many cases cancer cells develop chemoresistance to these treatments. Non‑thermal gas plasma (NTGP) was recently identified as a potential tool for cancer treatment. In this study, we investigated the potential use of NTGP to control SNUC5 human colon carcinoma cells. We hypothesized that NTGP would generate reactive oxygen species (ROS) in these cells, resulting in induction of endoplasmic reticulum (ER) stress. ROS generation, expression of ER stress‑related proteins and mitochondrial calcium levels were analyzed. Our results confirmed that plasma‑generated ROS induce apoptosis in SNUC5 cells. Furthermore, we found that plasma exposure resulted in mitochondrial calcium accumulation and expression of unfolded protein response (UPR) proteins such as glucose‑related protein 78 (GRP78), protein kinase R (PKR)‑like ER kinase (PERK), and inositol‑requiring enzyme 1 (IRE1). Elevated expression of spliced X‑box binding protein 1 (XBP1) and CCAAT/enhancer‑binding protein homologous protein (CHOP) further confirmed that ROS generated by NTGP induces apoptosis through the ER stress signaling pathway.