[신간의 별자리x] 우리/미술, 그리고 ‘슬픔의 박물관’

In mammals, cadmium is widely considered as a non-genotoxic carcinogen acting through a methylation-dependent epigenetic mechanism. Here, the effects of Cd treatment on the DNA methylation patten are examined together with its effect on chromatin reconfiguration in Posidonia oceanica. DNA methylation level and pattern were analysed in actively growing organs, under short- (6 h) and long- (2 d or 4 d) term and low (10 mM) and high (50 mM) doses of Cd, through a Methylation-Sensitive Amplification Polymorphism technique and an immunocytological approach, respectively. The expression of one member of the CHROMOMETHYLASE (CMT) family, a DNA methyltransferase, was also assessed by qRT-PCR. Nuclear chromatin ultrastructure was investigated by transmission electron microscopy. Cd treatment induced a DNA hypermethylation, as well as an up-regulation of CMT, indicating that de novo methylation did indeed occur. Moreover, a high dose of Cd led to a progressive heterochromatinization of interphase nuclei and apoptotic figures were also observed after long-term treatment. The data demonstrate that Cd perturbs the DNA methylation status through the involvement of a specific methyltransferase. Such changes are linked to nuclear chromatin reconfiguration likely to establish a new balance of expressed/repressed chromatin. Overall, the data show an epigenetic basis to the mechanism underlying Cd toxicity in plants.

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In Posidonia oceanica cadmium induces changes in DNA methylation and chromatin patterning

Several molecules present in the diet, including flavonoids, can inhibit the growth of cancer cells with an ability to act as "chemopreventers". Their cancer-preventive effects have been attributed to various mechanisms, including the induction of cell-cycle arrest and/or apoptosis as well as the antioxidant functions. The antioxidant activity of chemopreventers has recently received a great interest, essentially because oxidative stress participates in the initiation and progression of different pathological conditions, including cancer. Since antioxidants are capable of preventing oxidative damage, the wide use of natural food-derived antioxidants is receiving greater attention as potential anti-carcinogens. Among flavonoids, quercetin (Qu) is considered an excellent free-radical scavenging antioxidant, even if such an activity strongly depends on the intracellular availability of reduced glutathione. Apart from antioxidant activity, Qu also exerts a direct, pro-apoptotic effect in tumor cells, and can indeed block the growth of several human cancer cell lines at different phases of the cell cycle. Both these effects have been documented in a wide variety of cellular models as well as in animal models. The high toxicity exerted by Qu on cancer cells perfectly matches with the almost total absence of any damages for normal, non-transformed cells. In this review we discuss the molecular mechanisms that are based on the biological effects of Qu, and their relevance for human health.

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Quercetin and cancer chemoprevention.

Polyphenols, found abundantly in plants, display many anticarcinogenic properties including their inhibitory effects on cancer cell proliferation, tumor growth, angiogenesis, metastasis, and inflammation as well as inducing apoptosis. In addition, they can modulate immune system response and protect normal cells against free radicals damage. Most investigations on anticancer mechanisms of polyphenols were conducted with individual compounds. However, several studies, including ours, have indicated that anti-cancer efficacy and scope of action can be further enhanced by combining them synergistically with chemically similar or different compounds. While most studies investigated the anti-cancer effects of combinations of two or three compounds, we used more comprehensive mixtures of specific polyphenols and mixtures of polyphenols with vitamins, amino acids and other micronutrients. The mixture containing quercetin, curcumin, green tea, cruciferex, and resveratrol (PB) demonstrated significant inhibition of the growth of Fanconi anemia head and neck squamous cell carcinoma and dose-dependent inhibition of cell proliferation, matrix metalloproteinase (MMP)-2 and -9 secretion, cell migration and invasion through Matrigel. PB was found effective in inhibition of fibrosarcoma HT-1080 and melanoma A2058 cell proliferation, MMP-2 and -9 expression, invasion through Matrigel and inducing apoptosis, important parameters for cancer prevention. A combination of polyphenols (quercetin and green tea extract) with vitamin C, amino acids and other micronutrients (EPQ) demonstrated significant suppression of ovarian cancer ES-2 xenograft tumor growth and suppression of ovarian tumor growth and lung metastasis from IP injection of ovarian cancer A-2780 cells. The EPQ mixture without quercetin (NM) also has shown potent anticancer activity in vivo and in vitro in a few dozen cancer cell lines by inhibiting tumor growth and metastasis, MMP-2 and -9 secretion, invasion, angiogenesis, and cell growth as well as induction of apoptosis. The presence of vitamin C, amino acids and other micronutrients could enhance inhibitory effect of epigallocatechin gallate (EGCG) on secretion of MMPs. In addition, enrichment of NM with quercetin (EPQ mix) enhanced anticancer activity of NM in vivo. In conclusion, polyphenols, especially in combination with other polyphenols or micronutrients, have been shown to be effective against multiple targets in cancer development and progression, and should be considered as safe and effective approaches in cancer prevention and therapy.

https://www.mdpi.com/2072-6643/8/9/552/pdf

Anticancer Efficacy of Polyphenols and Their Combinations.

The present study focused on the elucidation of the putative anticancer potential of quercetin. The anticancer activity of quercetin at 10, 20, 40, 80 and 120 µM was assessed in vitro by MMT assay in 9 tumor cell lines (colon carcinoma CT‑26 cells, prostate adenocarcinoma LNCaP cells, human prostate PC3 cells, pheocromocytoma PC12 cells, estrogen receptor‑positive breast cancer MCF‑7 cells, acute lymphoblastic leukemia MOLT‑4 T‑cells, human myeloma U266B1 cells, human lymphoid Raji cells and ovarian cancer CHO cells). Quercetin was found to induce the apoptosis of all the tested cancer cell lines at the utilized concentrations. Moreover, quercetin significantly induced the apoptosis of the CT‑26, LNCaP, MOLT‑4 and Raji cell lines, as compared to control group (P<0.001), as demonstrated by Annexin V/PI staining. In in vivo experiments, mice bearing MCF‑7 and CT‑26 tumors exhibited a significant reduction in tumor volume in the quercetin‑treated group as compared to the control group (P<0.001). Taken together, quercetin, a naturally occurring compound, exhibits anticancer properties both in vivo and in vitro.

/pdf/anticancer-and-apoptosis-inducing-effects-of-quercetin-in-4tuh9m7bcx.pdf

Anticancer and apoptosis‑inducing effects of quercetin in vitro and in vivo

Quercetin is a flavonoid ubiquitously found in nature. The therapeutic effect of quercetin on human hepatoma cell line (HepG2) was evaluated in this study. Various groups were incubated with different doses of quercetin for 12-, 24-, 48- and 72-h time duration and compared with control groups. Dose- and time-dependent inhibition in HepG2 proliferation was found with quercetin treatment. At 48 h of incubation, 61.78% of the cells were arrested at G(1) phase with 25 microM/l quercetin while 89.62% were arrested at G(1) phase with 50 microM/l quercetin. Furthermore, the results indicate that quercetin increased the content of Cdk inhibitor p21 protein, which was correlated with the elevation in p53 levels during 12 h of incubation. In addition, quercetin also increased the level of Cdk inhibitor p27 protein during 24 h of incubation. From our results it can be concluded that quercetin blocks cell cycle progression at G(1) phase and exerts its growth-inhibitory effect through the increase of Cdk inhibitors p21 and p27 and tumor suppressor p53 in HepG2.

Quercetin induces cell cycle G1 arrest through elevating Cdk inhibitors p21 and p27 in human hepatoma cell line (HepG2).

Small heat shock proteins (smHSPs) play important and extensive roles in plant defenses against abiotic stresses. We cloned a gene for a smHSP from the David Lily (Lilium davidii (E. H. Wilson) Raffill var. Willmottiae), which we named LimHSP16.45 based on its protein molecular weight. Its expression was induced by many kinds of abiotic stresses in both the lily and transgenic plants of Arabidopsis. Heterologous expression enhanced cell viability of the latter under high temperatures, high salt, and oxidative stress, and heat shock granules (HSGs) formed under heat or salinity treatment. Assays of enzymes showed that LimHSP16.45 overexpression was related to greater activity by superoxide dismutase and catalase in transgenic lines. Therefore, we conclude that heterologous expression can protect plants against abiotic stresses by preventing irreversible protein aggregation, and by scavenging cellular reactive oxygen species.

/pdf/overexpression-of-small-heat-shock-protein-limhsp16-45-in-3dcn2f49bv.pdf

Overexpression of Small Heat Shock Protein LimHSP16.45 in Arabidopsis Enhances Tolerance to Abiotic Stresses

Plant meiotic prophase I is a complicated process involving the late zygotene and pachytene stages, both crucial for completing synapsis and recombination. Using David Lily (Lilium davidii var. Willmottiae) as our research material, we performed suppression subtractive hybridization to construct EST library of anthers at various stages of development by the pollen mother cells. From this library, we identified small heat shock protein LimHSP16.45 was highly expressed during the late zygotene to pachytene stages. Our results also showed that LimHSP16.45 was almost specifically expressed in the anther compared with the root, stem, or leaf, and in situ expression of LimHSP16.45 mRNAs showed strong signals in the pollen mother cells and tapetal cells. LimHSP16.45 could be induced by heat and cold in lily anthers, and its ectopic expression enhanced the viability of E. coli cells under both high and low temperatures. In vitro, it acted as molecular chaperone and could help luciferase refolding after heat shock stress. All of these data suggest that LimHSP16.45, working as molecular chaperone, possibly protects pollen mother cells and tapetal cells against extreme temperatures during late zygotene to pachytene stages of meiotic prophase I in David Lily.

Small heat shock protein LimHSP16.45 protects pollen mother cells and tapetal cells against extreme temperatures during late zygotene to pachytene stages of meiotic prophase I in David Lily

ELS1, a novel MATE transporter related to leaf senescence and iron homeostasis in Arabidopsis thaliana.

Auxin is important in the development of plant vascular tissues. Reconnection of vascular bundles between scion and stock is a primary aim of grafting, and polar auxin transport greatly affects the formation of a continuous vascular model. The role of auxin in the process of graft-union development was studied by grafting the seedlings of Arabidopsis thaliana (L.) Heynh. DR5:GUS marker plants, which exert the auxinspecific responses. Auxin induced the DR5:GUS expression in the vascular bundles around graft surface and stimulated the formation of multiple vascular bundle reconnections on the third day after grafting (DAG). DR5:GUS expression was delayed for one day in both scion and stock and dramatically declined by the auxin transport inhibitor N-1-naphthylphthalamic acid (NPA). Vascular bundle reconnection was observed only on the 4th DAG. These results suggest that auxin stimulates the reconnection of the vascular bundles, whereas NPA inhibits it. We studied the role of PIN proteins in graft development by grafting seedlings of PIN:GUS plants. PIN had different expression patterns in the graft process. Expression levels of PIN genes were analyzed by real-time PCR. All PIN genes had the higher expression level at the third DAG. We conclude that auxin stimulates the development of graft unions, and the patterns of expressions of PIN family genes can affect the development of graft-union by controlling the auxin flow.

Changjun Mu

Papers

Quercetin induces cell cycle G1 arrest through elevating Cdk inhibitors p21 and p27 in human hepatoma cell line (HepG2).

Overexpression of Small Heat Shock Protein LimHSP16.45 in Arabidopsis Enhances Tolerance to Abiotic Stresses

Small heat shock protein LimHSP16.45 protects pollen mother cells and tapetal cells against extreme temperatures during late zygotene to pachytene stages of meiotic prophase I in David Lily

ELS1, a novel MATE transporter related to leaf senescence and iron homeostasis in Arabidopsis thaliana.

Auxin redistribution and shifts in PIN gene expression during Arabidopsis grafting