Sae-Woong Kim

MicroRNA-29c functions as a tumor suppressor by direct targeting oncogenic SIRT1 in hepatocellular carcinoma

Mammalian sirtuin 1 (SIRT1) has connected to an ever widening circle of activities that encompass cellular stress resistance, energy metabolism and tumorigenesis. However, underlying mechanisms leading to oncogenic SIRT1 overexpression are less understood. In this study, we identified SIRT1 regulatory microRNA (miRNA) and its function in hepatocellular carcinoma (HCC). Aberrant SIRT1 overexpression was demonstrated in a subset of human HCCs. SIRT1 knockdown suppressed HCC cell growth by transcriptional deregulation of cell cycle proteins. This led to hypophosphorylation of pRb, which inactivated E2F/DP1 target gene transcription, and thereby caused significant increase of HCC cells to remain in the G1/S phase. A comprehensive miRNA profiling analysis indentified five putative endogenous miRNAs that are significantly downregulated in HCC. Ectopic expression of miRNA mimics evidenced miR-29c to suppress SIRT1 in HCC cells. Notably, ectopic miR-29c expression repressed cancer cell growth and proliferation, and it recapitulated SIRT1 knockdown effects in HCC cells. In addition, miR-29c expression was downregulated in a large cohort of HCC patients, and low expression of miR-29c was significantly associated with poor prognosis of HCC patients. Taken together, we demonstrated that miR-29c suppresses oncogenic SIRT1 by way of binding to 3′-untranslated region of SIRT1 mRNA causing translational inhibition in liver cancer cells. The loss or suppression of miR-29c may cause aberrant SIRT1 overexpression and promotes liver tumorigenesis. Overall, we suggest that miR-29c functions as a tumor suppressor by regulating abnormal SIRT1 activity in liver.

Anthocyanin Extracted from Black Soybean Reduces Prostate Weight and Promotes Apoptosis in the Prostatic Hyperplasia-Induced Rat Model

Anthocyanin is a natural plant pigment and potent antioxidant. This study was designed to investigate the effects of anthocyanin extracted from black soybeans on a rat model of benign prostatic hyperplasia (BPH), a disease associated with the geriatric population. Thirty male rats were divided into five experimental groups: a control group, a BPH-induced group, and three BPH-induced groups that received oral doses of anthocyanin (40, 80, and 160 mg/kg). Prostate hyperplasia was induced by the administration of testosterone propionate for 4 weeks. Following BPH induction, the anthocyanin-treated groups received the compound for 4 weeks. After anthocyanin treatment, the prostates from the rats in all groups were removed, weighed, and subjected to histological examination. Apoptosis in the prostates was measured by the TUNEL assay. The mean prostate weight for the control animals was 674.17 ± 28.24 mg, whereas the BPH-induced rats had a mean prostate weight of 1098.33 ± 131.31 mg. The mean prostate weights for the rats receiving 40, 80, and 160 mg/kg anthocyanin were 323.00 ± 22.41, 324.00 ± 26.80, and 617.50 ± 31.08 mg, respectively. The average prostate weight in the BPH-induced group was significantly higher than in the control group (p < 0.05), whereas the prostate weights in the anthocyanin-administered groups were significantly lower than in the BPH-induced group (p < 0.05). Injected testosterone led to prostatic hyperplasia as observed histologically, but anthocyanin administration helped to prevent this change. Apoptotic body counts were significantly higher in groups receiving anthocyanin than in the BPH-induced group (p < 0.05). These results suggest that anthocyanin may be effective in decreasing the volume and suppressing the proliferation of the prostate. Further studies are needed to better understand the mechanisms and actions of anthocyanin, and these studies may lead to the clinical application of anthocyanin in treating BPH.

The merlin tumor suppressor interacts with Ral guanine nucleotide dissociation stimulator and inhibits its activity

Neurofibromatosis type 2 (NF2) is the most commonly mutated gene in benign tumors of the human nervous system such as schwannomas and meningiomas. The NF2 gene encodes a protein called schwannomin or merlin, which is involved in regulating cell growth and proliferation through protein–protein interactions with various cellular proteins. In order to better understand the mechanism by which merlin exerts its function, yeast two-hybrid screening was performed and Ral guanine nucleotide dissociation stimulator (RalGDS), a downstream molecule of Ras, was identified as a merlin-binding protein. The direct interaction between merlin and RalGDS was confirmed both in vitro and in the NIH3T3 cells. The domain analyses revealed that the broad C-terminal region of merlin (aa 141–595) is necessary for the interaction with the C-terminal Ras-binding domain (RBD) of RalGDS. Functional studies showed that merlin inhibits the RalGDS-induced RalA activation, the colony formation and the cell migration in mammalian cells. These results suggest that merlin can function as a tumor suppressor by inhibiting the RalGDS-mediated oncogenic signals.

Cyanidin-3-O-β-D-Glucopyranoside Concentrated Materials from Mulberry Fruit Have a Potency to Protect Erectile Function by Minimizing Oxidative Stress in a Rat Model of Diabetic Erectile Dysfunction

Objective: The aim of this study was to evaluate the effect of cyanidin-3-O-β-D-glucopyranoside (C3G) concentrated materials from mulberry fruit on improvement and protection of erectile function. Materials and Methods: Sprague-Dawley rats (12 weeks old) were divided into three groups (n = 12 in each): normal control, diabetes mellitus (DM), and DM with C3G concentrated material treatment (DM + C3G). DM and DM + C3G group rats received a single injection of streptozotocin (50 mg/kg), and 4 weeks after induction of diabetes, the DM + C3G group rats were treated with daily concentrated material treatment (10 mg/kg) dissolved in water for 8 weeks. After 12 weeks of streptozotocin injections, the rats in each group underwent intracavernosal pressure measurement and then the corporal tissues were sampled. Results: The DM group rats showed markedly lower erectile parameters than those in the control group, whereas rats in the DM + C3G group showed improved erectile function by minimizing corporal apoptosis and increasing the expression of endothelial nitric oxide synthase (NOS) and neuronal NOS protein. A significant increase in 8-hydroxy-2-deoxyguanosine (8-OHdG) was shown in the DM group compared with the normal group. However, in the DM + C3G group, 8-OHdG was statistically significantly reduced compared with the DM group. Conclusions: The current study is the first to suggest that C3G concentrated materials may have a potency to improve and protect erectile function under conditions of diabetes-induced oxidative stress.

Evaluation of the biocompatibility of a coating material for an implantable bladder volume sensor

As the applications for implantable medical devices have increased, the need for biocompatible packaging materials has become important. Recently, we reported an implantable sensor for real‐time monitoring of the changes in bladder volume, which necessitated finding a safe coating material for use in bladder tissue. At present, materials like polyethylene glycol (PEG), polydimethylsiloxane (PDMS) and parylene‐C are used in biomedical devices or as coating materials, owing to their excellent safety in various medical fields. However, few studies have assessed their safety in bladder tissue, therefore, we evaluated the biocompatibility of PEG, PDMS and parylene‐C in the bladder. All three materials turned out to be safe in in vitro tests of live/dead staining and cell viability. In vivo tests with hematoxylin and eosin and immunofluorescence staining with MAC387 showed no persistent inflammation. Therefore, we consider that the three materials are biocompatible in bladder tissue. Despite this safety, however, PEG has biodegradable characteristics and thus is not suitable for use as packaging. We suggest that PDMS and parylene‐C can be used as safe coating materials for the implantable bladder volume sensor reported previously.

Protective effect of cyanidin‐3‐O‐β‐D‐glucopyranoside fraction from mulberry fruit pigment against oxidative damage in streptozotocin‐induced diabetic rat bladder

To determine whether cyanidin‐3‐O‐β‐D‐glucopyranoside (C3G) fraction from mulberry fruit pigment has protective effects against bladder dysfunction on streptozotocin‐induced diabetic rats

Reduction of oxidative stress may play a role in the anti-inflammatory effect of the novel herbal formulation in a rat model of hydrochloric acid-induced cystitis

We investigated the effect of the multi‐herbal medicine, WSY‐1075 in an animal model of hydrochloric acid (HCl)‐induced cystitis.

Seoritae Extract Reduces Prostate Weight and Suppresses Prostate Cell Proliferation in a Rat Model of Benign Prostate Hyperplasia

Seoritae is a type of black soybean that is known to have health-promoting effects due to its high isoflavone and anthocyanin contents. We evaluated whether Seoritae extract (SE) had beneficial effects on the reduction of prostate weight in a rat model of benign prostatic hyperplasia (BPH). BPH was induced by intramuscular injections of testosterone enanthate once a week for 5 weeks in Sprague-Dawley rats, and rats were treated with or without daily oral doses of SE during BPH induction. After 5 weeks, the oxidative stress (superoxide dismutase and 8-hydroxy-2-deoxyguanosine), apoptosis (caspase-3), and activity of 5-alpha reductase were evaluated in the serum and prostate. The SE treatment group showed a significant decrease in prostate weight, oxidative stress, apoptosis, and 5-alpha reductase activity compared to the nontreated BPH group. These results show that SE is effective in decreasing the weight and proliferation of the prostate, and suggest that SE may be an effective treatment for BPH.