• Asian Pacific Journal of Cancer Prevention
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• 제17권1호
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• pp.109-115
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• 2016

Background: P53 has been reported to be involved with tumorigenesis and has also been implicated as a significant biomarker in oral squamous cell carcinoma(OSCC). However, the diagnostic value of p53 antibodies remains controversial; hence, we comprehensively and quantitatively assessed the potential in the present systematic review. Materials and Methods: A comprehensive search was performed using PubMed and Embase, up to October 31, 2014, without language restriction. Studies were assessed for quality using QUADAS (quality assessment of studies of diagnostic accuracy). The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were pooled separately and compared with overall accuracy measures using diagnostic odds ratios (DORs) and symmetric summary receiver operating characteristic (SROC) curves. Results: Of 150 studies initially identified, 7 eligible regarding serum p53 antibodies met the inclusion criteria. Some 85.7% (6/7) were of relatively high quality (QUADAS $score{\geq}7$). The summary estimates for quantitative analysis of serum p53 antibody in the diagnosis of squamous cell carcinoma were: PLR 2.06 [95% confidence interval (CI) : 1.35-3.15], NLR 0.85 (95%CI: 0.80-0.90) and DOR 2.47 (95%CI: 1.49-4.12). Conclusions: This meta-analysis suggests that the use of s-p53-antibodies has potential diagnostic value with relatively high sensitivity and specificity for OSCC particularly with serum specimens for discrimination of OSCCs from healthy controls. However, its discrimination power is not perfect because of low sensitivity.

• Asian Pacific Journal of Cancer Prevention
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• 제15권13호
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• pp.5201-5205
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• 2014

Emodin, a natural anthraquinone isolated from the traditional Chinese medicine Radix rhizoma Rhei, can induce apoptosis in many kinds of cancer cells. This study demonstrated that emodin induces apoptosis in human colon cancer HCT116 cells by provoking oxidative stress, which subsequently triggers a p53-mitochondrial apoptotic pathway. Emodin induced mitochondrial transmembrane potential loss, increase in Bax and decrease in Bcl-2 expression and mitochondrial translocation and release of cytochrome c to cytosol in HCT116 cells. In response to emodin-treatment, ROS increased rapidly, and subsequently p53 was overexpressed. Pretreatment with the antioxidant NAC diminished apoptosis and p53 overexpression induced by emodin. Transfecting p53 siRNA also attenuated apoptosis induced by emodin, Bax expression and mitochondrial translocation being reduced compared to treatment with emodin alone. Taken together, these results indicate that ROS is a trigger of emodin-induced apoptosis in HCT116 cells, and p53 expression increases under oxidative stress, leading to Bax-mediated mitochondrial apoptosis.

• BMB Reports
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• 제49권9호
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• pp.497-501
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• 2016

Wide-line ¹H NMR intensity and differential scanning calorimetry measurements were carried out on the intrinsically disordered 73-residue full transactivation domain (TAD) of the p53 tumor suppressor protein and two peptides: one a wild type p53 TAD peptide with a helix pre-structuring property, and a mutant peptide with a disabled helix-forming propensity. Measurements were carried out in order to characterize their water and ion binding characteristics. By quantifying the number of hydrate water molecules, we provide a microscopic description for the interactions of water with a wild-type p53 TAD and two p53 TAD peptides. The results provide direct evidence that intrinsically disordered proteins (IDPs) and a less structured peptide not only have a higher hydration capacity than globular proteins, but are also able to bind a larger amount of charged solute ions.

• 동의생리병리학회지
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• 제19권3호
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• pp.628-632
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• 2005

The aim of this study was to investigate the cytotoxic effect and its mechanism on Radix Aconiti(RA) extract in lung cancer cell lines. RA extract treatment decreased the cell viability in a dose-dependent fashions in lung cancer cells including A549, H460, H23 and H157 cells. Many investigators reported that A549 and H460 cells expressed wild-type p53, but H23 and H157 cells preserved mutated p53. After treatment with RA extract in A549 and H460 cells, we measured the expression of p53 protein levels using Western blot. analysis. In both cells treated with RA extracts, p53 protein expressions were increased in a dose-dependent manner. In our experiments, RA extracts also have cytotoxic effects in H23 and H157, which have mutated p53. Treatment with RA extract decreased bcl-2 protein expressions in both cells. These results suggest that RA extracts have cytotoxic effects via p53 expression increase and bcl-2 inhibitable pathways in A549, H460 cells and H23, H157 cells, respectively.

• 한국전통의학지
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• 제15권1호
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• pp.106-112
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• 2006

The aim of this study was to investigate the cytotoxic effect and its mechanism on Radix Aconiti(RA) extract in lung cancer cell lines. RA extract treatment decreased the cell viability in a dose-dependent fashions in lung cancer cells including A549, H460, H23 and H157 cells. Many investigators reported that A549 and H460 cells expressed wild-type p53, but H23 and H157 cells preserved mutated p53. After treatment with RA extract in A549 and H460 cells, we measured the expression of p53 protein levels using Western blot. analysis. In both cells treated with RA extracts, p53 protein expressions were increased in a dose-dependent manner. In our experiments, RA extracts also have cytotoxic effects in H23 and H157, which have mutated p53. Treatment with RA extract decreased bcl-2 protein expressions in both cells. These results suggest that RA extracts have cytotoxic effects via p53 expression increase and bcl-2 inhibitable pathways in A549, H460 cells and H23, H157 cells, respectively.

• BMB Reports
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• 제52권2호
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• pp.157-162
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• 2019

Our previous study found that two novel cancer-related genes, PRR11 and SKA2, constituted a classic gene pair that was regulated by p53 and NF-Y in lung cancer. However, their role and regulatory mechanism in breast cancer remain elusive. In this study, we found that the expression levels of PRR11 and SKA2 were upregulated and have a negative prognotic value in breast cancer. Loss-of-function experiments showed that RNAi-mediated knockdown of PRR11 and/or SKA2 inhibited proliferation, migration, and invasion of breast cancer cells. Mechanistic experiments revealed that knockdown of PRR11 and/or SKA2 caused dysregulation of several downstream genes, including CDK6, TPM3, and USP12, etc. Luciferase reporter assays demonstrated that wild type p53 significantly repressed the PRR11-SKA2 bidirectional promoter activity, but not NF-Y. Interestingly, NF-Y was only essential for and correlated with the expression of PRR11, but not SKA2. Consistently, adriamycin-induced (ADR) activation of endogenous p53 also caused significant repression of the PRR11 and SKA2 gene pair expression. Notably, breast cancer patients with lower expression levels of either PRR11 or SKA2, along with wild type p53, exhibited better disease-free survival compared to others with p53 mutations and/or higher expression levels of either PRR11 or SKA2. Collectively, our study indicates that the PRR11 and SKA2 transcription unit might be an oncogenic contributor and might serve as a novel diagnostic and therapeutic target in breast cancer.

• 대한두경부종양학회지
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• 제22권1호
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• pp.15-22
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• 2006

Objectives: The salivary gland tumor shows heterogeneity in histologic patterns and biological behavior. The aim of this study is to elucidate the relationships between apoptosis and expressions of apoptosis-related factors(bcl-2, bax, M30), p53 and MIB-1 in the salivary gland tumors. Methods: Immunohistochemical stains for apoptosis-related factors, p53 and MIB-1 and TUNEL study for apoptosis were performed in 46 cases of salivary gland tumors 02 benign and 34 malignant). Results: Twenty(43.5%) of 46 cases showed positive reaction for apoptosis, and the expression rates of bcl-2, bax, M30, p53 and MIB-1 were 85.3%, 68.8%, 65.9%, 39.1% and 26.1%, respectively. A significant difference between benign and malignant tumors was only noted in MIB-1 expression(p=0.0167). In malignant tumors, apoptosis showed no significant relationships to expressions of apoptosis-related factors. There were inverse relationships between p53 and bcl-2 expression(p=0.0375), and between M30 and MIB-1 expressions(p=0.0379). No significant differences of apoptosis, bcl-2, bax, M30, p53 and MIB-1 expression rates according to the tumor size, lymph node status, recurrence and survival were found. Conclusion: In the development of benign and malignant salivary gland tumors, apoptosis might be associated, however, apoptosis and expressions of apoptosis-related factors seemed to be not reliable prognostic factors in malignant salivary gland tumors.

• Asian Pacific Journal of Cancer Prevention
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• 제15권3호
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• pp.1375-1379
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• 2014

Background: Differences in clinicopathological characteristics of gastric cancer (GC) between young and older patients are controversial and a matter of debate. Determining the statistical significance of clinicopathological information with respect to age might provide clues for better management and treatment ofGC. Materials and Methods: A total ofl03 Indiao GC patients were enrolled for study and specimens were classified according to the AjCC-TNM system. Patients were grouped into two age-wise categories, young patients (<40 years; n=13) and older patients (${\geq}40$ years, n=90). The clinicopathological features of both groups were retrospectively examined and compared. p53 alterations were analyzed by polymerase chain reaction-single strand conformational polymorphism and immunohistochemistry methods at gene and protein levels respectively. The cases were considered p53 over-expressed if it was present in more than 25% of the tumor cells and p53 alterations was correlated with the clinicopathological characteristics of the patients as well as etiological factors for GC in both groups. Results: We found significant association of young patients with cancer stage (p=0.01), and very strong association with histology grade (p=0.064) and poorly differentiated (p=0.051) state of GC. However, neither young nor elderly patients showed associations with location, gender, etiological factors and p53 expression and alteration. Overall the male-to-female ratio of GC patients was 3.12 and the value was higher in the young (5.5) than in the older group (2.91). Conclusions: Clinicopathological features of GC like caocer stage, cell differentiation and histological grades were significantly different among young and old age cohorts. We observed a male predominance among the young group that decreased significantly with advancing age. More awareness of GC onset is required to detect cancer at an early stage for successful treatment.

• BMB Reports
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• 제55권2호
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• pp.92-97
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• 2022

Lysine methylation is one of the most important histone modifications that modulate chromatin structure. In the present study, the roles of the histone lysine demethylases JMJD2a and LSD1 in CK2 downregulation-mediated senescence were investigated. The ectopic expression of JMJD2a and LSD1 suppressed the induction of senescence-associated β-galactosidase activity and heterochromatin foci formation as well as the reduction of colony-forming and cell migration ability mediated by CK2 knockdown. CK2 downregulation inhibited JMJD2a and LSD1 expression by activating the mammalian target of rapamycin (mTOR)-ribosomal p70 S6 kinase (p70S6K) pathway. In addition, the down-regulation of JMJD2a and LSD1 was involved in activating the p53-p21^Cip1/WAF1-SUV39h1-trimethylation of the histone H3 Lys9 (H3K9me3) pathway in CK2-downregulated cells. Further, CK2 downregulation-mediated JMJD2a and LSD1 reduction was found to stimulate the dimethylation of Lys370 on p53 (p53K370me2) and nuclear import of SUV39h1. Therefore, this study indicated that CK2 downregulation reduces JMJD2a and LSD1 expression by activating mTOR, resulting in H3K9me3 induction by increasing the p53K370me2-dependent nuclear import of SUV39h1. These results suggest that CK2 is a potential therapeutic target for age-related diseases.

• 생명과학회지
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• 제21권5호
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• pp.753-760
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• 2011

본 연구는 파프리카 추출물과 그 성분인 비타민 C, 라이코펜과 베타-카로틴이 UVB (ultraviolet-B)에 의한 유전독성의 감소에 효과를 보이는 지를 HaCaT 세포를 이용하여 분석하였다. 자외선을 조사하지 않은 정상 세포의 세포활성은 파프리카 추출물을 경우 처리하지 않은 대조군과 차이를 나타내지 않았지만 비타민 C의 경우 농도 의존적으로 증가시키는 것을 관찰하였다. 그러나 라이코펜과 베타-카로틴의 경우 농도 의존적으로 점차 세포활성이 감소하는 것으로 관찰되었다. UVB로 상해받은 세포를 추출물이나 그 성분으로 후 배양할 경우 정상 배양액으로 배양한 대조군에 비해 파프리카 추출물과 비타민C은 농도 의존적으로 세포 활성을 증가시켰으나 라이코펜과 베타-카로틴의 경우 농도 의존적으로 감소키는 것을 관찰할 수 있었다. 자외선을 조사하지 않은 정상 세포의 핵 분절율은 파프리카 추출물과 비타민 C의 경우 대조군과 유의적인 차이를 나타내지 않았지만, 라이코펜, 베타-카로틴의 경우 농도 의존적으로 핵 분절율이 증가하는 것을 관찰하였다. UVB를 조사한 후 파프리카 추출물이나 비타민 C를 처리한 경우 정상 배양액으로 배양한 대조군에 비해 핵 분절율을 감소시켰지만 라이코펜과 베타-카로틴의 경우 농도 의존적으로 증가시켰다. 세포 상해에 반응하는 유전자인 p53과 GADD45의 단백질 수준을 Western blot으로 분석한 결과, 파프리카 추출물만 처리했을 경우 p53과 GADD45 단백질 수준은 처리하지 않은 대조군과 비교해서 유의미한 차이를 나타내지 않았으나 UVB를 조사한 후 파프리카 추출물을 처리한 경우 농도 의존적으로 p53 단백질 발현량이 감소하였다. 비타민 C를 단독 처리할 경우 대조군에 비해 p53과 GADD45 단백질 발현량은 감소하였으며, UVB를 조사한 후 비타민 C를 처리한 경우에도 농도 의존적으로 p53과 GADD45 단백질 발현량이 감소하는 것을 확인할 수 있었다. 그러나 라이코펜과 베타-카로틴만 단독 처리할 경우 p53과 GADD45 단백질 발현량이 처리하지 않은 대조군에 비해 농도 의존적으로 증가하였다. UVB를 조사한 후 베타-카로틴을 처리한 경우에도 상대적인 고농도에서 p53과 GADD45 단백질 발현량이 증가하는 것을 확인할 수 있었다. 위의 결과를 토대로 파프리카 추출물과 비타민 C는 UVB에 의해 손상된 세포의 세포 독성을 회복하는 효능이 있다고 생각된다. 라이코펜과 베타-카로틴의 경우에는 UVB에 의해 발현된 p53 단백질의 수준이 농도 의존적으로 더욱 증가하는 것으로 보아 UVB에 의한 세포고사가 라이코펜과 베타-카로틴에 의해 강화되는 것으로 생각된다.