• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5363-5369
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• 2012

High-risk human papillomavirus (HPV) especially HPV-16 and HPV-18 types are speculated to be important risk factors in non-smoking associated lung cancer in Asia. Increasing evidence has demonstrated that HPV oncoproteins may contribute to lung tumorigenesis and cell transformation. Importantly, HPV 16/18 E6 and E7 oncoproteins can mediate expression of multiple target genes and proteins, such as p53/pRb, VEGF, HIF-$1{\alpha}$, cIAP-2, and hTERT, and contribute to cell proliferation, angiogenesis and cell immortalization through different signaling pathways in lung cancer. This article provides an overview of experiment data on HPV-associated lung cancer, describes the main targets on which HPV E6/E7 oncoproteins act, and further discusses the potential signaling pathways in which HPV E6/E7 oncoproteins are involved. In addition, we also raise questions regarding existing problems with the study of HPV-associated lung cancer.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.53 no.spc
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• pp.65-71
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• 2008

The effect of rice bran (RB) applied alone or in combination with chemical fertilizer at different application rate on the phytochemical and antioxidant properties of rice was investigated. The treatments were 3 levels of RB namely: 200% RB (500 kg $10a^{-1}$), 100% RB (250 kg $10a^{-1}$), 50% RB (125 kg $10a^{-1}$), Recommended fertilizer dose (RF: $N-{P_2}{O_5}{K_2}O$, 11-5.5-4.8 kg $10a^{-1}$) combined with each RB, Half-recommended fertilizer dose (HRF: $N-{P_2}{O_5}{K_2}O$, 5.5-2.75-2.4 kg $10a^{-1}$) combined with each RB, RF and HRF applied at 1, 5, 10 days before rice transplanting (DBT). The parameters investigated were antioxidant, phytosterol and fatty acid contents. Results showed that the antioxidant property and phytosterol contents were high at 10 DBT HRF plus RB, 5 DBT RF plus RB, and 1 DBT 100 and 200% RB. However, total polyphenols increased from 10 to 1 DBT. In the case of fatty acids, no general trend was observed between treatments at different application times. Linoleic acid was high at 10 DBT HRF plus RB while linolenic acid was not affected at different application times. Palmitoeic and oleic acids were not also affected at 5 and 10 DBT. Saturated fatty acids were not also affected by any treatment at different application times except for palmitic acid.Most parameters obtained higher values at 100 and 200% RB treatments in 1 DBT.

• The Journal of Korean Obstetrics and Gynecology
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• v.19 no.2
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• pp.214-225
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• 2006

Purpose : This study was aimed to investigate the inhibitory effect of Corydalis Tuber on the proliferation of human uterine leiomyoma cell and the expression of gene related the mechanism of cell apoptosis. Methods : We counted the number of suvival cells treated with indicated concentration of Corydalis Tuber and investigated cell viability by MTS assay. Furthermore, flow cytometric analyis were used to dissect between necrosis and apoptosis related with cell cycle and then we observed the differential gene expression by western blot analysis. Results : 1) The inhibitory effect on the proliferation of uterine leiomyoma cell treated with Corydalis Tuber was increased in a concentration and time proportional. 2) The result of flow cytometry analysis, subG1 phase arrest related cell apoptosis was not investigated in uterine leiomyoma cell treated Corydalis Tuber but showed G2/M phase prolongation. 3) The gene expression of p27, p21 related cell cycle was increased according to increasing concentration, but p53 was not exchanged. 4) The dephosphorylation of pRb gene were increased dependent on treatment concentration and pro-caspase 3, CDK4 were not exchanged. Conclusion : This study showed that Corydalis Tuber have the inhibitory effect on the proliferation of human uterine leiomyoma cell but the effect was thoughted no relationship with apoptosis. The inhibitory effect was suggested that dephosphorylation of pRb gene induced with increasing p21, p27 prolonged cell division in G2/M phase.

• Journal of Ginseng Research
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• v.23 no.3 s.55
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• pp.190-197
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• 1999

In this study, the molecular mechanism of the growth inhibitory effect of panaxynol was investigated in a human malignant melanoma cell line, SK-MEL-l. In the cell cycle analysis, panaxynol arrested cell cycle progression of SK-MEL-I at the G1 phase. Immunoblot analysis demonstrated that panaxynol increased $p21^{WAF1}$ and decreased cdc2 expression. Protein levels of pl6, p27, E2F-1, Rb, and p53 were not changed. Thus, the changes in expression levels of $p21^{WAF1}$ and cdc2 apparently mediate the cell cycle arrest caused by panaxynol. In addition, cycloheximide (CHX) partially reversed the growth inhibition by panaxynol, which suggested that new protein synthesis was required. On the other hand, LLnL, a proteasome inhibitor, increased antiproliferative effect of panaxynol. This may be due to stabilization of the protein(s) responsible for the growth inhibition such as $p21^{WAF1}$. In summary, these results demonstrate that panaxynol inhibits proliferation of SK-MEL-I by inducing cell cycle arrest at the G1 phase and the inhibitory effect is mediated by the increased level of $p21^{WAF1}$ as well as decreased cdc2 expression.

• Tuberculosis and Respiratory Diseases
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• v.42 no.2
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• pp.123-129
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• 1995

장차 세포증식과 분화의 전환에 있어서 세포주기의 구성요소들과 Rb 사이의 상호관계 및 세포주기의 조절과 DNA 손상에 대한 p53의 역할을 함께 상세하게 �P혀야 한다. 형질전환된 경우에는 p16과 p21을 포함하여 관련된 CDI들에 의한 cyclin과 CDK의 복합체의 조절에 있어서 중요한 변화들을 야기시키므로 CDI들의 불활성과 발암현상과의 정확한 인과관계를 �P혀내야 한다. 발아 또는 분열효모균에서 Sic 1과 Rum 1과 같은 cyclin-CDK의 중요한 조절인자들이 확인되었는데, 포유동물에 있어서 이러한 단백들에 대한 대응물들을 기대해보며, 체크포인트와 세포사망기전 및 암세포들에 있어서 탈조절에 대한 이해가 새로운 항암치료제 개발에 중요하다고 생각된다.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.27 no.6
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• pp.483-490
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• 2001

There were many controversies in the cause and progress of tumorigenesis. Recently, studies on the mutation of genes related to the tumor have extensively been performed due to development of molecular biology. Structural and morphological changes of chromosomes, which are related to the abnormal activation of oncogenes or inactivation of tumor suppression genes, transform the normal cells into the tumor cells. p53 and Rb are well known tumor suppressor genes, while oncogenes include c-myc, bcl-2 and ras, etc. When exposed to cell damaging agents, p53 inhibits cell growth by inducing transcription of p21. Especially p73, which is homo-logy of p53, frequently deleted in melanoma, neuroblastoma, colon cancer, and breast cancer, when over produced, p73 activates the transcription of p21, bax-1 and inhibits cell growth by inducing apoptosis. For study on mRNA expression of p21 and p73, normal oral keratinocytes, and cell lines of primary and metastatic oral squamous cell carcinoma were cultured and then electrophoresis and RT-PCR(reverse transcription-polymerase chain reaction) were performed. 1. The mRNA of p21 and p73 in normal oral keratinocyte expressed lower than that of primary squamous cell carcinoma. 2. The mRNA of p21 in metastatic oral squamous carcinoma cell lines was expressed as various patterns compared with that of normal oral keratinocyte. 3. In the metastatic oral squamous cell lines, the mRNA of HN8 expressed higher than that of HN12 or HN19. 4. The mRNA of p73 in primary oral squamous cell lines expressed 4-5 times higher than that of normal keratinocyte. 5. In metastatic oral squamous cell lines, there was no significant expression of p73 mRNA compared with that of normal oral keratinocyte. From the results obtained in this study, mRNA expression of p73 in primary oral squamous cell lines was remarkable, while mRNA expression of p21 and p73 in metastatic oral squamous cell lines were statistically insignificant.

• Journal of Periodontal and Implant Science
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• v.31 no.3
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• pp.597-610
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• 2001

Normal gingival fibroblasts functioning is fundamental for the maintenance of periodontal connective tissue as well as wound healing. Nicotine have been found to affect DNA synthesis and cell proliferation, which appear to depend on the type of cells. This in vitro study was done to determine the effects of nicotine, a major component of tobacco, on cell proliferation, viability, activity, cell cycle distribution, and expression of cell cycle regulatory proteins in human gingival fibroblasts. Nicotine has been tested for 2 days or 4 days in 5 different concentrations; $0.1{\mu}g/ml$; $1{\mu}g/ml$; $10{\mu}g/ml$; $100{\mu}g/ml$; $1000{\mu}g/ml$. To assess cell proliferation and viability, viable and non-viable cells were counted by hemocytometer; to evaluate cellular activity, MTT assay was employed; to analyze cell cycle distribution, fluorescent propidium iodide-DNA complex were measured using fluorocytometer; to determine the expression of cell cycle regulatory proteins, western blot analysis was performed. After 2 days and 4 days incubation respectively, at concentrations of $1{\mu}g/ml$ - $1000{\mu}g/ml$, nicotine significantly inhibited proliferation comparing to non-supplemented controls. The cell viability was significantly decreased after 2 days and 4 days at concentrations of $1{\mu}g/ml$ - $1000{\mu}g/ml$ and at $10{\mu}g/ml$ - $1000{\mu}g/ml$ respectively. After 2 days and 4 days, the cellular activity was significantly decreased at concentrations of $10{\mu}g/ml$ - $1000{\mu}g/ml$. Treatment with $100{\mu}g/ml$ nicotine for 48 hours caused an increase in the proportion of G1-phase cells (from 46.41% to 53.46%) and a decrease in the proportion of S-phase cells (from 17.80% to 14.27%). The levels of cyclin $D_1$ and CDK 4 proteins in nicotine-treated fibroblasts were lower than that of controls, whereas the levels of p16 and pRB were higher than that of controls. These results suggest that the decrease of cell proliferation and lengthened Gap phases (G1) by nicotine may due to the increased expression of p16 and pRB as well as decreased expression of cyclin $D_1$ and CDK 4 in human gingival fibroblasts.

• Journal of Periodontal and Implant Science
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• v.31 no.1
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• pp.135-148
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• 2001

Gingival fibroblasts are major cellular component of gingiva. However, the molecular mechanisms of senescence of human gingival fibroblasts are unknown. Human fibroblasts undergo replicative senescence in vitro after a limited number of population doublings. A reduced rate of proliferation is a prominent phenomenon observed in senescent fibroblasts. This phenomenon is controled by cell cycle regulatory proteins. The purpose of present study was to investigate the effect of replicative senescence on cell cycle progression and to find out its molecular mechanisms in human gingival fibroblasts. Replicative senescence of gingival fibroblasts were induced by subsequent cultures that were repeated up to 18 passage. In the present study, I examined change of cell proliferation, cell activity, cell viability and cell cycle progression during the replicative process. Also, I examined expression of cell cycle regulatory proteins which was estimated by western blot analysis. Cell proliferation, cell activity and cell viability of gingival fibroblasts were notably decreased with increase of population doubling level(PDL). S phase was decreased and G1 phase was increased with increase of PDL. Western blot analysis showed that levels of P16, p21 and p53 of senescent gingival fibroblasts(PDL41, PDL58) were higher than young fibroblasts(PDL27) and cdk4 were lower than young fibroblasts(PDL27). In conclusion, these results suggest that proliferative function of human gingival fibroblasts may be decreased by replicative senescence and its molecular mechanisms may be activatied with p16, p21, p53 and pRB, and repressed wtih cdk4.

• BMB Reports
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• v.53 no.8
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• pp.419-424
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• 2020

Bee venom (BV), secreted from the venom gland of the honey bee, contains several biological active compounds. BV has been widely used as a traditional medicine for treating human disease, including cancer. In this study, we have shown the molecular mechanism underlying the therapeutic effect of BV on cancer. Treatment with BV reduced the proliferation of cervical-cancer cells in a dose- and time-dependent manner. Interestingly, the killing effect of BV was specific to HPV-positive cervical-cancer cell lines, such as Caski and HeLa cells, and not to HPV-negative cervical-cancer cells (C33A). BV reduced the expression of HPV E6 and E7 at RNA and protein levels, leading to an increase in the expression of p53 and Rb in Caski and HeLa cells. Further, BV decreased the levels of cell-cycle proteins, such as cyclin A and B, and increased the levels of cell-cycle inhibitors, such as p21 and p27. BV significantly induced apoptosis and inhibited wound healing and migration of cervical-cancer cells. It also upregulated the expression of pro-apoptotic BAX and downregulated the expression of anti-apoptotic Bcl-2 and Bcl-XL. Cleavage of caspase-3, caspase-9, and PARP were also induced by BV treatment, whereas the phosphorylation of mitogenic signaling-related proteins, such as AKT, JNK, p38, and ERK, were downregulated. Our results indicate that BV has a therapeutic selectivity for HPV-positive malignant cells, so further clinical studies are needed to assess its clinical application.

• Korean Journal of Plant Resources
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• v.32 no.6
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• pp.714-722
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• 2019

Oxidative DNA damage negatively affects humans and the research is currently ongoing to find ways to reduce oxidative stress. Oxidative stress has been identified as a key factor in triggering various diseases. Thus, its alleviation is important for human health. Broussonetia kazinoki (B. kazinoki) has been used in traditional Korean medicine as a dermatological therapy to treat burns, pruritus, and acne. B. kazinoki is generally segregated into peeled root (PR), root bark (RB), peeled stem (PS), and stem bark (SB). To assess these components for their antioxidant activity and protection against DNA damage, their ethyl acetate fractions were examined by 1,1-diphenyl-2-picryl hydrazyl (DPPH) and 2,2'-Azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical scavenging assay. As a result of confirming the expression of factors involved in attenuating DNA damage, the protective effect of SB on oxidative stress suppressed the expression of p-p53 and γ-H2AX. Additionally, the levels of p53 and H2AX mRNA were significantly downregulated. In conclusion, these results indicated that the SB component of B. kazinoki had the potential to be used as an effective natural antioxidant compared to the other parts of the plant.