• Title/Summary/Keyword: p-53

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Synergistic Effects of 5-Fluorouracil (FU) and Curcumin on Human Cervical Cancer Cells (5-fluorouracil과 curcumin의 복합투여에 의한 자궁암세포의 성장억제와 p53유전자 발현의 상승 효과)

  • Ahn, Seong-Ho;Kim, Dong-Heui;Kang, Jung-Hoon;Lee, Myeong-Seon
    • Applied Microscopy
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    • v.40 no.4
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    • pp.229-235
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    • 2010
  • Cervical cancer is associated with low antioxidant status. It has a high prevalence especially amongst woman in Asia and is a leading cause of cancer death. Cancer chemotherapy in vivo improved in cases with high p53 expression in the tumor tissue. The restoration of p53 levels could be a potential strategy to increase chemoresponsiveness. Under circumstances where damage is extensive, p53 plays a direct role in trigering apoptosis. To investigate the effect of curcumin (CMN) as an antioxidant agent on anticancer agent 5-fluorouracil (5FU) induced apoptosis and p53 expression, HPV-18 positive HeLa cells were treated with noncytotoxic amounts of antioxidant. Curcumin induced apoptosis in cervical cancer cells. Morphological hallmarks of apoptosis such as nuclear fragmentation and internucleosomal fragmentation of DNA were observed. CMN caused upregulation of p53 expression, evident from Western blotting data and also increased the susceptibility/apoptosis induced by 5FU. These results show that increasing drug sensitivity of cervical cancer cells by upregulation of p53 using CMN is novel approach and could have a possible therapeutic potential in cervical cancer.

Functional Role of a Conserved Sequence Motif in the Oxygen-dependent Degradation Domain of Hypoxia-inducible Factor 1α in the Recognition of p53

  • Chi, Seung-Wook
    • Genomics & Informatics
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    • v.6 no.2
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    • pp.72-76
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    • 2008
  • Hypoxia-inducible factor $1{\alpha}\;(HIF1{\alpha})$ is a transcription factor that plays a key role in the adaptation of cells to low oxygen stress and oxygen homeostasis. The oxygen-dependent degradation (ODD) domain of $HIF1{\alpha}$ is responsible for the negative regulation of $HIF1{\alpha}$ in normoxia. The interactions of the $HIF1{\alpha}$ ODD domain with partner proteins such as von Hippel-Lindau tumor suppressor (pVHL) and p53 are mediated by two sequence motifs, the N- and C-terminal ODD(NODD and CODD). Multiple sequence alignment with $HIF1{\alpha}$ homologs from human, monkey, pig, rat, mouse, chicken, frog, and zebrafish has demonstrated that the NODD and CODD motifs have noticeably high conservation of the primary sequence across different species and isoforms. In this study, we carried out molecular dynamics simulation of the structure of the $HIF1{\alpha}$ CODD motif in complex with the p53 DNA-binding domain (DBD). The structure reveals specific functional roles of highly conserved residues in the CODD sequence motif of $HIF1{\alpha}$ for the recognition of p53.

Ubiquitination of p53 is Involved in Troglitazone Induced Apoptosis in Cervical Cancer Cells

  • Chen, Hui-Min;Zhang, Ding-Guo;Wu, Jin-Xiz;Pei, Dong-Sheng;Zheng, Jun-Nian
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.5
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    • pp.2313-2318
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    • 2014
  • Peroxisome proliferator-activated receptor gamma (PPAR-${\gamma}$), a ligand-dependent nuclear transcription factor, has been found to widely exist in tumor tissues and plays an important role in affecting tumor cell growth. In this study, we investigated the effect of PPAR-${\gamma}$ on aspects of the cervical cancer malignant phenotype, such as cell proliferation and apoptosis. Cell growth assay, Western blotting, Annexin V and flow cytometry analysis consistently showed that treatment with troglitazone (TGZ, a PPAR-${\gamma}$ agonist) led to dose-dependent inhibition of cervical cancer cell growth through apoptosis, whereas T0070907 (another PPAR-${\gamma}$ antagonist) had no effect on Hela cell proliferation and apoptosis. Furthermore, we also detected the protein expression of p53, p21 and Mdm2 to explain the underlying mechanism of PPAR-${\gamma}$ on cellular apoptosis. Our work, finally, demonstrated the existence of the TGZ-PPAR-${\gamma}$-p53 signaling pathway to be a critical regulator of cell apoptosis. These results suggested that PPAR-${\gamma}$ may be a potential therapeutic target for cervical cancer.

Tumor suppressor Parkin induces p53-mediated cell cycle arrest in human lung and colorectal cancer cells

  • Byung Chul Jung;Sung Hoon Kim;Yoonjung Cho;Yoon Suk Kim
    • BMB Reports
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    • v.56 no.10
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    • pp.557-562
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    • 2023
  • Dysregulation of the E3 ubiquitin ligase Parkin has been linked to various human cancers, indicating that Parkin is a tumor suppressor protein. However, the mechanisms of action of Parkin remain unclear to date. Thus, we aimed to elucidate the mechanisms of action of Parkin as a tumor suppressor in human lung and colorectal cancer cells. Results showed that Parkin overexpression reduced the viability of A549 human lung cancer cells by inducing G2/M cell cycle arrest. In addition, Parkin caused DNA damage and ATM (Ataxia telangiectasia mutated) activation, which subsequently led to p53 activation. It also induced the p53-mediated upregulation of p21 and downregulation of cyclin B1. Moreover, Parkin suppressed the proliferation of HCT-15 human colorectal cancer cells by a mechanism similar to that in A549 lung cancer cells. Taken together, our results suggest that the tumor-suppressive effects of Parkin on lung and colorectal cancer cells are mediated by DNA damage/p53 activation/cyclin B1 reduction/cell cycle arrest.

Neuroprotective Effect of Resveratrol on Acute Brain Ischemia Reperfusion Injury by Measuring Annexin V, p53, Bcl-2 Levels in Rats

  • Kizmazoglu, Ceren;Aydin, Hasan Emre;Sevin, Ismail Ertan;Kalemci, Orhan;Yuceer, Nurullah;Atasoy, Metin Ant
    • Journal of Korean Neurosurgical Society
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    • v.58 no.6
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    • pp.508-512
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    • 2015
  • Background : Cerebral ischemia is as a result of insufficient cerebral blood flow for cerebral metabolic functions. Resveratrol is a natural phytoalexin that can be extracted from grape's skin and had potent role in treating the cerebral ischemia. Apoptosis, a genetically programmed cellular event which occurs after ischemia and leads to biochemical and morphological changes in cells. There are some useful markers for apoptosis like Bcl-2, bax, and p53. The last reports, researchers verify the apoptosis with early markers like Annexin V. Methods : We preferred in this experimental study a model of global cerebral infarction which was induced by bilateral common carotid artery occlusion method. Rats were randomly divided into 4 groups : sham, ischemia-reperfusion (I/R), I/R plus 20 mg/kg resveratrol and I/R plus 40 mg/kg resveratrol. Statistical analysis was performed using Sigmastat 3.5 ve IBM SPSS Statistics 20. We considered a result significant when p<0.001. Results : After administration of resveratrol, Bcl-2 and Annexin levels were significantly increased (p<0.001). Depending on the dose of resveratrol, Bcl2 levels increased, p53 levels decreased but Annexin V did not effected. P53 levels were significantly increased in ishemia group, so apoptosis is higher compared to other groups. Conclusion : In the acute period, Annexin V levels misleading us because the apoptotic cell counts could not reach a certain level. Therefore we should support our results with bcl-2 and p53.

Chromosome Imbalances and Alterations in the p53 Gene in Uterine Myomas from the Same Family Members: Familial Leiomyomatosis in Turkey

  • Hakverdi, Sibel;Demirhan, Osman;Tunc, Erdal;Inandiklioglu, Nihal;Uslu, Inayet Nur;Gungoren, Arif;Erdem, Duygu;Hakverdi, Ali Ulvi
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.2
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    • pp.651-658
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    • 2013
  • Uterine leiomyomas (UL) are extremely common neoplasms in women of reproductive age, and are associated with a variety of characteristic choromosomal aberrations (CAs). The p53 gene has been reported to play a crucial role in suppressing the growth of a variety of cancer cells. Therefore, the present study investigated the effects of CAs and the p53 gene on ULs. We performed cytogenetic analysis by G-banding in 10 cases undergoing myomectomy or hysterectomy. Fluorescence in situ hybridization (FISH) with a p53 gene probe was also used on interphase nuclei to screen for deletions. In patients, CAs were found in 23.4% of 500 cells analysed, significantly more frequent than in the control group (p<0.001). In the patients, 76% of the abnormalities were structural aberrations (deletions, translocations and breaks), and only 24% were numerical. Deletions were the most common structural aberration observed in CAs. Among these CAs, specific changes in five loci 1q11, 1q42, 2p23, 5q31 and Xp22 have been found in our patients and these changes were not reported previously in UL. The chromosome breaks were more frequent in cases, from high to low, 1, 2, 6, 9, 3, 5, 10 and 12. Chromosome 22, X, 3, 17 and 18 aneuploidy was observed to be the most frequent among all numerical aberrations. We observed a low frequency of p53 losses (2-11%) in our cases. The increased incidence of autosomal deletions, translocations, chromatid breaks and aneuploidy, could contribute to the progression of the disease along with other chromosomal alterations.

p53, Cyclin D1, p21 (WAF1) and Ki-67 (MIB1) Expression at Invasive Tumour Fronts of Oral Squamous Cell Carcinomas and Development of Local Recurrence

  • Sawair, F;Hassona, Y;Irwin, C;Stephenson, M;Hamilton, P;Maxwell, P;Gordon, D;Leonard, A;Napier, S
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.3
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    • pp.1243-1249
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    • 2016
  • Background: Expression of p53, cyclin D1, p21 (WAF1) and Ki-67 (MIB1) was evaluated in oral squamous cell carcinoma (OSCC) to test whether levels of these markers at invasive tumour fronts (ITFs) could predict the development of local recurrence. Materials and Methods: Archived paraffin-embedded specimens from 51 patients with T1/T2 tumours were stained immunohistochemically and analysed quantitatively. Local recurrence-free survival was tested with Kaplan-Meier survival plots (log-rank test) using median values to define low and high expression groups and with a Cox's proportional hazards model in which the expression scores were entered as continuous variables. Results: The assessment of expression of all markers was highly reliable, univariate analysis showing that patients with clear surgical margins, with low cyclin D1 and high p21 expression at the ITF had the best local recurrence-free survival. Multivariate analysis showed that these three parameters were independent prognostic factors but that neither p53 nor MIB1 expression were of prognostic value. Conclusions: Assessment of p53, cyclin D1, p21 (WAF1), and Ki-67 (MIB1) at the ITF could help to predict local recurrence in early stage oral squamous cell carcinoma cases.

The Polynomial Numerical Index of Lp(μ)

  • Kim, Sung Guen
    • Kyungpook Mathematical Journal
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    • v.53 no.1
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    • pp.117-124
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    • 2013
  • We show that for 1 < $p$ < ${\infty}$, $k$, $m{\in}\mathbb{N}$, $n^{(k)}(l_p)=inf\{n^{(k)}(l^m_p):m{\in}\mathbb{N}\}$ and that for any positive measure ${\mu}$, $n^{(k)}(L_p({\mu})){\geq}n^{(k)}(l_p)$. We also prove that for every $Q{\in}P(^kl_p:l_p)$ (1 < $p$ < ${\infty}$), if $v(Q)=0$, then ${\parallel}Q{\parallel}=0$.