BACKGROUND: Malvidin is one of the most abundant components in red wines and black rice. The effects of malvidin on aging and lifespan under oxidative stress have not been fully understood. This study focused on the anti-aging effect of malvidin on stress-induced premature senescence (SIPS) in WI-38 human lung-derived diploid fibroblasts. METHODS: In order to determine the viability of WI-38 cells, MTT assay was conducted, and malondialdehyde level was determined using thiobarbituric acid-reactive substance assay. Protein expression of inflammation-related factors was also evaluated by Western blot analysis. RESULTS: Acute and chronic oxidative stress via hydrogen peroxide (H2O2) treatment led to SIPS in WI-38 cells, which showed decreased cell viability, increased lipid peroxidation, and a shortened lifespan in comparison with non-H2O2-treated WI-38 cells. However, malvidin treatment significantly attenuated H2O2-induced oxidative stress by inhibiting lipid peroxidation and increasing cell viability. Furthermore, the lifespan of WI-38 cells was prolonged by malvidin treatment. In addition, malvidin downregulated the expression of oxidative stress-related proteins, including NF-κB, COX-2, and inducible nitric oxide synthase. Furthermore, protein expression levels of p53, p21, and Bax were also regulated by malvidin treatment in WI-38 cells undergoing SIPS. CONCLUSIONS: Malvidin may potentially inhibit the aging process by controlling oxidative stress.
Aging* ; Blotting, Western ; Cell Survival ; Diploidy ; Fibroblasts* ; Humans* ; Hydrogen Peroxide ; Lipid Peroxidation ; Malondialdehyde ; Nitric Oxide Synthase Type II ; Oxidative Stress ; Wine

BACKGROUND: Despite recent advances in therapy, colorectal cancer still has a grim prognosis. Although licorice has been used in East Asian traditional medicine, the molecular properties of its constituents including dehydroglyasperin D (DHGA-D) remain unknown. We sought to evaluate the inhibitory effect of DHGA-D on colorectal cancer cell proliferation and identify the primary signaling molecule targeted by DHGA-D. METHODS: We evaluated anchorage-dependent and -independent cell growth in HT-29 human colorectal adenocarcinoma cells. The target protein of DHGA-D was identified by Western blot analysis with a specific antibody, and direct interaction between DHGA-D and the target protein was confirmed by kinase and pull-down assays. Cell cycle analysis by flow cytometry and further Western blot analysis was performed to identify the signaling pathway involved. RESULTS: DHGA-D significantly suppressed anchorage-dependent and -independent HT-29 colorectal cancer cell proliferation. DHGA-D directly suppressed phosphatidylinositol 3-kinase (PI3K) activity and subsequent Akt phosphorylation and bound to the p110 subunit of PI3K. DHGA-D also significantly induced G1 cell cycle arrest, together with the suppression of glycogen synthase kinase 3β and retinoblastoma phosphorylation and cyclin D1 expression. CONCLUSIONS: DHGA-D has potent anticancer activity and targets PI3K in human colorectal adenocarcinoma HT-29 cells. To our knowledge, this is the first report to detail the molecular basis of DHGA-D in suppressing colorectal cancer cell growth.
Adenocarcinoma ; Blotting, Western ; Cell Cycle ; Cell Proliferation ; Colorectal Neoplasms* ; Cyclin D1 ; Flow Cytometry ; G1 Phase Cell Cycle Checkpoints ; Glycogen Synthase Kinases ; Glycyrrhiza ; HT29 Cells ; Humans* ; Medicine, East Asian Traditional ; Phosphatidylinositol 3-Kinase* ; Phosphatidylinositols* ; Phosphorylation ; Phosphotransferases ; Prognosis ; Retinoblastoma

Graphic warning labels (GWLs) have been developed as a representative non-price policy to block such marketing. This study investigated the current state and effect of the global introduction of GWLs and examines the future tasks related to GWLs. We systematically reviewed literatures on GWL and a tobacco control strategy in the past fifteen years. The policy of enforcing GWLs has spread globally based on the Framework Convention on Tobacco Control. GWLs are more effective than text warnings and are implemented in over 70 countries. The policy has showed the impact of GWLs as a preventive effect on adolescents' smoking, inducement of smoking cessation, reduction in the amount of tobacco smoked, and reduction in smoking rates. The success of an anti-smoking policy can manifests itself as an effect of individual policies, the rise of tobacco prices, and the introduction of GWLs.
Health Policy ; Health Promotion ; Internationality* ; Marketing ; Smoke* ; Smoking Cessation ; Smoking* ; Tobacco ; Tobacco Products* ; Tobacco Use

Generation of reactive oxygen species (ROS) by diverse anti-cancer drugs or phytochemicals has been closely related with the induction of apoptosis in cancers. Also, the downregulation of ROS by these chemicals has been found to block initiation of carcinogenesis. Therefore, modulation of ROS by phytochemicals emerges as a crucial mechanism to regulate apoptosis in cancer prevention or therapy. This review summarizes the current understanding of the selected chemical compounds and related cellular components that modulate ROS during apoptotic process. Metformin, quercetin, curcumin, vitamin C, and other compounds have been shown to downregulate ROS in the cellular apoptotic process, and some of them even induce apoptosis in cancer cells. The cellular components mediating the downregulation of ROS include nuclear factor erythroid 2-related factor 2 antioxidant signaling pathway, thioredoxin, catalase, glutathione, heme oxygenase-1, and uncoupling proteins. The present review provides information on the relationship between these compounds and the cellular components in modulating ROS in apoptotic cancer cells.
Apoptosis* ; Ascorbic Acid ; Carcinogenesis ; Catalase ; Curcumin ; Down-Regulation* ; Glutathione ; Heme Oxygenase-1 ; Metformin ; Negotiating ; Phytochemicals ; Quercetin ; Reactive Oxygen Species* ; Thioredoxins

Nitric oxide (NO) in general plays a beneficial physiological role as a vasorelaxant and the role of NO is decided by its concentration present in physiological environments. NO either facilitates cancer-promoting characters or act as an anti-cancer agent. The dilemma in this regard still remains unanswered. This review summarizes the recent information on NO and its role in carcinogenesis and tumor progression, as well as dietary chemopreventive agents which have NO-modulating properties with safe cytotoxic profile. Understanding the molecular mechanisms and cross-talk modulating NO effect by these chemopreventive agents can allow us to develop better therapeutic strategies for cancer treatment.
Carcinogenesis ; Chemoprevention* ; Nitric Oxide Synthase Type II ; Nitric Oxide Synthase Type III ; Nitric Oxide*

Apigenin (4′,5,7-trihydroxyflavone) is a flavonoid commonly found in many fruits and vegetables such as parsley, chamomile, celery, and kumquats. In the last few decades, recognition of apigenin as a cancer chemopreventive agent has increased. Significant progress has been made in studying the chemopreventive aspects of apigenin both in vitro and in vivo. Several studies have demonstrated that the anticarcinogenic properties of apigenin occur through regulation of cellular response to oxidative stress and DNA damage, suppression of inflammation and angiogenesis, retardation of cell proliferation, and induction of autophagy and apoptosis. One of the most well-recognized mechanisms of apigenin is the capability to promote cell cycle arrest and induction of apoptosis through the p53-related pathway. A further role of apigenin in chemoprevention is the induction of autophagy in several human cancer cell lines. In this review, we discuss the details of apigenin, apoptosis, autophagy, and the role of apigenin in cancer chemoprevention via the induction of apoptosis and autophagy.
Apigenin* ; Apium graveolens ; Apoptosis* ; Autophagy* ; Cell Cycle Checkpoints ; Cell Line ; Cell Proliferation ; Chamomile ; Chemoprevention ; DNA Damage ; Fruit ; Humans ; In Vitro Techniques ; Inflammation ; Oxidative Stress ; Petroselinum ; Rutaceae ; Vegetables

Cancer cells rewire their metabolism to satisfy the demands of growth and survival, and this metabolic reprogramming has been recognized as an emerging hallmark of cancer. Lipid metabolism is pivotal in cellular process that converts nutrients into energy, building blocks for membrane biogenesis and the generation of signaling molecules. Accumulating evidence suggests that cancer cells show alterations in different aspects of lipid metabolism. The changes in lipid metabolism of cancer cells can affect numerous cellular processes, including cell growth, proliferation, differentiation, and survival. The potential dependence of cancer cells on the deregulated lipid metabolism suggests that enzymes and regulating factors involved in this process are promising targets for cancer treatment. In this review, we focus on the features associated with the lipid metabolic pathways in cancer, and highlight recent advances on the therapeutic targets of specific lipid metabolic enzymes or regulating factors and target-directed small molecules that can be potentially used as anticancer drugs.
Lipid Metabolism ; Lipogenesis ; Membranes ; Metabolic Networks and Pathways ; Metabolism

Bone destruction induced by the metastasis of breast cancer cells is a frequent complication that is caused by the interaction between cancer cells and bone cells. Receptor activator of nuclear factor kappa-B ligand (RANKL) and the endogenous soluble RANKL inhibitor, osteoprotegerin (OPG), directly play critical roles in the differentiation, activity, and survival of osteoclasts. In patients with bone metastases, osteoclastic bone resorption promotes the majority of skeletal-related events and propagates bone metastases. Therefore, blocking osteoclast activity and differentiation via RANKL inhibition can be a promising therapeutic approach for cancer-associated bone diseases. We investigated the potential of isoliquiritigenin (ISL), which has anti-proliferative, anti-angiogenic, and anti-invasive effects, as a preventive and therapeutic agent for breast cancer cell-induced bone destruction. ISL at non-toxicity concentrations significantly inhibited the RANKL/OPG ratio by reducing the production of RANKL and restoring OPG production to control levels in hFOB1.19 cells stimulated with conditioned medium (CM) of MDA-MB-231 cells. In addition, ISL reduced the expression of cyclooxygenase-2 in hFOB1.19 cells stimulated by CM of MDA-MB-231 cells. Therefore, ISL may have inhibitory potential on breast cancer-induced bone destruction.
Bone Diseases ; Bone Resorption ; Breast Neoplasms* ; Breast* ; Culture Media, Conditioned ; Cyclooxygenase 2 ; Humans* ; Neoplasm Metastasis ; Osteoblasts* ; Osteoclasts ; Osteoprotegerin ; RANK Ligand

BACKGROUND: The role of tumour inflammation and the dysplastic epithelial-stromal interactions on the nature of collagen fibres in the extracellular matrix of dysplastic epithelium is not fully understood. The present study was aimed to evaluate and compare the inflammation and pathological stromal collagen (loosely packed thin disorganized collagen) present in mild, moderate and severe epithelial dysplasias with that of inflammatory fibrous hyperplasias. The basement membrane intactness of epithelial dysplasias was also evaluated to determine if dysplastic epithelial mesenchymal interaction has any role in the integrity of stromal collagen in epithelial dysplasia. METHODS: Oral epithelial dysplasias, inflammatory fibrous hyperplasia and normal oral mucosal samples were used for the study. Packing, thickness and orientation of collagen fibres in mild, moderate and severe grades of oral epithelial dysplasias (n = 24), inflammatory fibrous hyperplasia (n = 8) and normal oral mucosal samples (n = 8) were analysed based on the polarisation of collagen fibres in picrosirius red polarising stain under polarising microscope. RESULTS: All the grades of epithelial dysplasias showed greenish yellow birefringence confirming the presence of loosely arranged pathological collagen in the presence of moderate inflammation. All the cases of inflammatory fibrous hyperplasia showed red polarisation hue and moderate inflammation. A statistically significant difference was found in the packing and orientation of collagen when epithelial dysplasias and inflammatory fibrous hyperplasia were compared (P < 0.01). When the intactness of basement membrane integrity was compared in all the groups of epithelial dysplasia, a statistically significant result was obtained (P < 0.05). CONCLUSIONS: Presence of significant amount of loosely packed thin disoriented collagen even in mild epithelial dysplasia suggests that tumourigenic factors are released to connective tissue stroma much earlier than expected. Hence we suggest considering the integrity of extracellular matrix collagen, intactness of basement membrane and inflammation associated with dysplasia along with the anaplasia of epithelial cells in the microscopic assessment of dysplastic epithelium.
Anaplasia ; Basement Membrane ; Birefringence ; Collagen* ; Connective Tissue ; Epithelial Cells ; Epithelium ; Extracellular Matrix* ; Hyperplasia* ; Inflammation* ; Microscopy* ; Mouth Mucosa

BACKGROUND: A microRNA, miR-34a, plays a key role in inhibiting cellular transformation and carcinogenesis by controlling cell cycle regulation and cell proliferation in various human tumors. However, miR-34a has rarely been reported in endometrial cancer research in Korea. This study was undertaken to analyze miR-34a expression in simple endometrial hyperplasia and endometrial cancer, and to evaluate the relationship between expression of miR-34a and p16 and Ki-67 proteins in endometrial cancers. METHODS: A retrospective study was carried out on 66 formalin-fixed, paraffin-embedded tissues with simple endometrial hyperplasia (31 cases) and endometrial cancer (35 cases) patients. These were analyzed for miR-34a expression by quantitative real-time PCR , and the expression of p16 and Ki-67 proteins in endometrial cancers was evaluated by immunohistochemistry. RESULTS: The miR-34a expression level was lower in endometrial cancer tissues (??.71 +/- 3.90) than in simple endometrial hyperplasia tissues (2.68 +/- 8.62). The endometrial hyperplasia tissues showed underexpression of miR-34a in 13 of the 31 cases (41.9%) while the endometrial cancer tissues showed underexpression of miR-34a in 24 of 35 cases (68.6%). Thus, miR-34a was significantly underexpressed in endometrial cancer tissues when compared endometrial hyperplasia tissues (P = 0.046). Overexpression of p16 was detected in 25 (71.4%) and Ki-67 immunoreactivity was detected in 27 (77.1%) of the 35 endometrial cancers. Although not statistically significant, the frequency of p16 and Ki-67 overexpression tended to be lower in the cases with miR-34a underexpression than in cases with miR-34a overexpression. CONCLUSIONS: These findings suggest that underexpression of miR-34a might be involved in endometrial carcinogenesis. Further studies are needed to define the relationship between miR-34a expression and tissue specific protein expression.
Carcinogenesis* ; Cell Cycle ; Cell Proliferation ; Endometrial Hyperplasia ; Endometrial Neoplasms* ; Female ; Humans ; Immunohistochemistry ; Korea ; MicroRNAs ; Real-Time Polymerase Chain Reaction ; Retrospective Studies