• Biomolecules & Therapeutics
• /
• v.25 no.4
• /
• pp.396-403
• /
• 2017

Under normal, non-stressed conditions, intracellular p53 is continually ubiquitinated by MDM2 and targeted for degradation. However, in response to severe genotoxic stress, p53 protein levels are markedly increased and apoptotic cell death is triggered. Inhibiting the ubiquitination of p53 under conditions where DNA damage has occurred is therefore crucial for preventing the development of cancer, because if cells with severely damaged genomes are not removed from the population, uncontrolled growth can result. However, questions remain about the cellular mechanisms underlying the regulation of p53 stability. In this study, we show that p53-inducible gene 3 (PIG3), which is a transcriptional target of p53, regulates p53 stability. Overexpression of PIG3 stabilized both endogenous and transfected wild-type p53, whereas a knockdown of PIG3 lead to a reduction in both endogenous and UV-induced p53 levels in p53-proficient human cancer cells. Using both in vivo and in vitro ubiquitination assays, we found that PIG3 suppressed both ubiquitination- and MDM2-dependent proteasomal degradation of p53. Notably, we demonstrate that PIG3 interacts directly with MDM2 and promoted MDM2 ubiquitination. Moreover, elimination of endogenous PIG3 in p53-proficient HCT116 cells decreased p53 phosphorylation in response to UV irradiation. These results suggest an important role for PIG3 in regulating intracellular p53 levels through the inhibition of p53 ubiquitination.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.12
• /
• pp.6349-6355
• /
• 2012

Previous studies showed that Math1 homologous to human Hath1 can cause mouse goblet cells to differentiate. In this context it is important that the majority of colon cancers have few goblet cells. In the present study, the potential role of Hath1 in colon carcinogenesis was investigated. Sections of paraffin-embedded tissues were used to investigate the goblet cell population of normal colon mucosa, mucosa adjacent colon cancer and colon cancer samples from 48 patients. Hath1 and Muc2 expression in these samples were tested by immunohistochemistry, quantitative real-time reverse transcription -PCR and Western blotting. After the recombinant plasmid, pcDNA3.1(+)-Hath1 had been transfected into HT29 colon cancer cells, three clones were selected randomly to test the levels of Hath1 mRNA, Muc2 mRNA, Hath1, Muc2, cyclin D1 and p27 by quantitative real-time reverse transcription-PCR and Western blotting. Moreover, the proliferative ability of HT29 cells introduced with Hath1 was assessed by means of colony formation assay and xenografting. Expression of Hath1, Muc2, cyclin D1 and p27 in the xenograft tumors was also detected by Western blotting. No goblet cells were to be found in colon cancer and levels of Hath1 mRNA and Hath1, Muc2 mRNA and Muc2 were significantly down-regulated. Hath1 could decrease cyclin D1, increase p27 and Muc2 in HT29 cells and inhibit their proliferation. Hath1 may be an anti-oncogene in colon carcinogenesis.

• Archives of Pharmacal Research
• /
• v.28 no.9
• /
• pp.1047-1052
• /
• 2005

Two phenolic glucosides, eutigoside Band eutigoside C were isolated from the fresh leaves of Eurya emarginata. These two phenolic glucosides exerted a significant inhibitory effect on the growth of HL-60 promyelocytic leukemia cells. Furthermore, when the HL-60 cells were treated with eutigoside C, several apoptotic characteristics such as DNA fragmentation, morphologic changes, and increase of the population of sub-G1 hypodiploid cells were observed. In order to understand the mechanism of apoptosis induction by eutigoside C, we examined the changes of Bcl-2 and Bax expression levels. The eutigoside C reduced BcI-2 protein and mRNA levels, but slightly increased Bax protein and mRNA levels in a time-dependent manner. When we examined the activation of caspase-3, an effector of apoptosis, the eutigoside C increased the expression of active form (19-kDa) of caspase-3 and the increase of their activities was demonstrated by the cleavage of poly (ADP-ribose) polymerase, a substrate of caspase-3, to 85-kDa. The results suggest that the inhibitory effect of eutigoside C from E. emarginata on the growth of HL-60 appears to arise from the induction of apoptosis via the down-regulation of BcI-2 and the activation of caspase.

• Journal of Environmental Health Sciences
• /
• v.43 no.2
• /
• pp.130-142
• /
• 2017

Objectives: Although the Korean government is able to implement smoke-free regulations for shared areas in multi-unit housing (MUH), such regulations are limited for private homes. The purpose of this study was to determine the prevalence and predictors of support for the implementation of smoke-free regulations for homes and near the outsides of building among residents in MUH. Methods: A population-based sample of 2,600 residents among a web-based panel in Seoul was included. The residents completed questionnaires including smoking status, voluntary smoke-free home rules, and support for the implementation of smoke-free regulations for homes and near the outsides of building. The presence of a voluntary smoke-free home rule was determined when residents declared that no one smoked inside their homes. Results: Among the 2,600 MUH residents, prevalence of support for the implementation of smoke-free regulations for homes was higher (83.2%) than for near the outsides of buildings (75.1%). Support for the implementation of smoke-free regulations for homes was higher when residents were non-smokers, had voluntary smoke-free home rules, lived with children, lived with more residents, lived in owned homes, lived in apartments, and lived in homes with more frequent secondhand smoke (SHS) incursion. Support for the implementation of smoke-free regulations near the outsides of buildings was higher when residents were women, non-smokers, more educated, had a voluntary smoke-free home rule, lived with children, lived in homes with more frequent SHS incursion, and lived in a commercial area. Conclusions: The majority was supportive of the implementation of smoke-free regulations for homes. Predictors identified in the study can be useful for promoting implementation of smoke-free regulations for homes in MUH.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.10
• /
• pp.5113-5117
• /
• 2012

Prohibitin (PHB) is a chaperone protein which is highly conserved evolutionarily. It shows significant homology with the Drosophila cc gene which is considered important for development and differentiation of Drosophila melanogaster. Investigations have revealed an involvement of PHB in cellular proliferation and development, apoptosis, signal transduction, mitochondrial function and regulation of the estrogen and androgen receptors. Therefore, we conducted the present study to analyze mutations in the highly conserved region in Indian female breast cancer patients. Conventional PCR-SSCP and Automated DNA sequencing were performed with a total of 105 breast cancer samples along with adjacent normal tissue. Of the total, 14.2% (15/105) demonstrated a mutation status of prohibitin observed in our study population. We identified a novel missense mutation (Thr>Ser), a novel deletion of T nucleotide in an intron adjacent to intron-exon boundary and a previously determined missense mutation (Val>Ala). A statistically significant correlation was obtained which suggested that prohibitin may be associated with tumor development and/or progression of at least some proportion of breast cancers.

• Journal of Korean Society of Occupational and Environmental Hygiene
• /
• v.9 no.1
• /
• pp.1-13
• /
• 1999

Even though there is no fit test regulations in Korea, in many developed countries, respirator fit testing is required before entering specific work environment to ensure that the respirator worn satisfies a minimum of fit and that the user knows when the respirator fits properly. Due to no regulation for fit test, a lot of Korean workers wearing respirators may be potentially exposed to hazards. Anthropometric test panels for testing the fit of respirators are very important to develop respirators fitted properly for Korean workers. To evaluate the fitting performance, 304 workers (272 males, 32 females) and 536 students (268 male, 268 females) were fit tested for 4 full-facepieces (2 domestic-made S, C, and 2 foreign-made T, N), 2 half masks (1 domestic-made S, and 1 foreign-made T) and 3 quarter masks (2 domestic-made S, C, and 1 foreign-made T) with PortaCount 8020. Fit factors of foreign-made masks were higher than those of domestic-made masks in all types. Males were fitted more properly than females. A facial dimension survey of 364 workers (339 males, 25 females) and 158 students (69 males, 89 females) was conducted to develop test panels for fit testing. Subjects were selected on the basis of face length and face width to wear full-facepiece masks in test. For testing half- and quarter masks, face length and lip length were used. Test panels containing 25 male-and-female subjects and 16 male subjects were respectively developed for full-facepiece, and half-and quarter masks to represent a majority of population surveyed.

• Journal of Life Science
• /
• v.12 no.2
• /
• pp.129-135
• /
• 2002

Several kinds of thermophilic, aerobic microorganisms (Bacillus genus), metal leaching microorganisms (Thiobacillus, T. ferooxidans), and other nondegradable chemical-degrading microorganisms (Pseudomonas genus) were utilized to study the effect on composting livestock manure. Under the Carbon-Nitrogen ratio (C/N) of 35∼40 and water content of 50∼65% conditions, the composting in the cycling drum reactor showed slower composting and lower temperature increase than that of the manual reactor. Element analysis after composting indicated relatively high levels of mineral contents with the substitutional effect of chemical fertilizer. Metal analysis before and after composting showed lower As in all, Cr in pig, Pb in cow, Hg in chicken, and Cu in cow manure compost than the regulation values. Compost maturity was ascertained by the several maturity tests. Salmonella and E. cozi detection test by SS or EMB agar plate confirmed the safety from the pathogenic microorganisms. The results suggest that the inoculation of metal and some other chemical degrading microorganisms during composting might decrease metal contamination and increase composting rate.

• Korean Journal of Pharmacognosy
• /
• v.40 no.1
• /
• pp.59-64
• /
• 2009

Atopic dermatitis, caused by immune hyper-responsiveness, is wide spread in humans as well as in the dogs, especially in industrialized condition. Pet dogs are generally exposed to the same environment as their owners, and a significant portion of these animals are also known to suffer from this allergic disease. However, diagnosis and treatment methods of atopic dermatitis in animals have not been well established. We explored the possibility of using recently developed PG102 for the treatment of atopic dermatitis in the canine population. PG102 is a water soluble extract prepared from Actinidia arguta, and has been shown to produce significant therapeutic effect in variable allergy animal models. After oral administration of PG102 at a dose of 12.5 mg/kg daily for 4 weeks, severity of disease was greatly improved. IgE is one of representative members used to diagnose allergic diseases in humans. However, it is not well established whether there is any correlation between the serum level of IgE and atopic dermatitis. Our data indicated that dogs diagnosed to have atopic dermatitis contained higher level of serum IgE than the normal dogs and that treatment of dogs with PG102 significantly lowered the serum level of IgE. Taken together, this study demonstrated that PG102 treatment yielded significant amelioration of canine atopic dermatitis and down-regulation of serum IgE and that the serum level of IgE can be used as a convenient member for diagnosis of atopic dermatitis in dogs.

• Korean Journal of Pharmacognosy
• /
• v.40 no.1
• /
• pp.65-69
• /
• 2009

The present study investigated the antiproliferative effect of Litsea japonica in HL-60/ADR, adriamycin resistant human promyelocytic leukemia cells. The 80% ethanol extract of L. japonica markedly inhibited the growth of HL-60/ADR cells. When HL-60/ADR cells were treated with the extract, several apoptosis events like as DNA fragmentation, chromatin condensation and the increase of the population of sub-G1 hypodiploid cells were observed. In the mechanism of apoptosis induction by L. japonica, we examined the changes of Bcl-2 and Bax protein expression levels, and activation of caspases. After the HL-60/ADR cells were treated with the extract, the Bcl-2 expression was decreased, whereas the expression of Bax was increased in a time-dependent manner compared to the control. In addition, the active forms of caspase-9 and -3 were increased and the cleavage of poly (ADP-ribose) polymerase, a vital substrate of effector caspase, was observed. The results suggest that the inhibitory effect of L. japonica on the growth of the HL-60/ADR appears to arise from the induction of apoptosis via the down-regulation of Bcl-2 and the activation of caspases.

• Biomolecules & Therapeutics
• /
• v.20 no.1
• /
• pp.81-88
• /
• 2012

Histone deacetylases (HDACs) are enzymes involved in the remodelling of chromatin, and have a key role in the epigenetic regulation of gene expression. Histone deacetylase (HDAC) inhibitors are emerging as an exciting new class of potential anti-cancer agents. In recent years, a number of structurally diverse HDAC inhibitors have been identifi ed and these HDAC inhibitors induce growth arrest, differentiation and/or apoptosis of cancer cells in vitro and in vivo. However, the underlying molecular mechanisms remain unclear. This study aimed at investigating the anti-tumor activity of various HDAC inhibitors, IN-2001, using T47D human breast cancer cells. Moreover, the possible mechanism by which HDAC inhibitors exhibit anti-tumor activity was also explored. In estrogen receptor positive T47D cells, IN-2001, HDAC inhibitor showed anti-proliferative effects in dose-and time-dependent manner. In T47D human breast cancer cells showed anti-tumor activity of IN-2001 and the growth inhibitory effects of IN-2001 were related to the cell cycle arrest and induction of apoptosis. Flow cytometry studies revealed that IN-2001 showed accumulation of cells at $G_2$/M phase. At the same time, IN-2001 treatment time-dependently increased sub-$G_1$ population, representing apoptotic cells. IN-2001-mediated cell cycle arrest was associated with induction of cdk inhibitor expression. In T47D cells, IN-2001 as well as other HDAC inhibitors treatment significantly increased $p21^{WAF1}$ and $p27^{KIP1}$ expression. In addition, thymidylate synthase, an essential enzyme for DNA replication and repair, was down-regulated by IN-2001 and other HDAC inhibitors in the T47D human breast cancer cells. In summary, IN-2001 with a higher potency than other HDAC inhibitors induced growth inhibition, cell cycle arrest, and eventual apoptosis in human breast cancer possibly through modulation of cell cycle and apoptosis regulatory proteins, such as cdk inhibitors, cyclins, and thymidylate synthase.