• Korean Journal of Head & Neck Oncology
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• v.18 no.1
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• pp.23-29
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• 2002

Mutation of the P53 tumor suppressor gene playa major role in the development of many carcinomas, namely in the colon, breast and bladder, whereas the role played by such mutations in thyroid carcinogenesis remains controversial. Vascular endothelial growth factor (VEGF) induces proliferation of endothelial cells, stimulates angiogenesis, and increases vascular permeability. Increased VEGF expression has been associated with poor clinical outcomes in many malignancies E-cadherin, a calcium-dependent transmembrane glycoprotein, is an adhesion molecule Expression of p53, VEGF and E-cadherin was assessed immunohistochemically in 19 tall columnar variant of papillary carcinoma, 24 common papillary carcinoma and 7 follicular carcinoma. The aim of this study was to evaluate the expression of P53,VEGF and E-cadherin as a potential maker for the prognosis of thyroid carcinomas. The results are as follows: 1) There were no significance in any clinical parameters examined among tall columnar variant of papillary carcinoma, common papillary carcinoma and follicular carcinoma. 2) The expression of P53 demonstrated low in tall columnar variant of papillary carcinoma, common papillary carcinoma and follicular carcinoma, but a significantly high in regional lymph node metastasis. 3) The expression of VEGF demonstrated a significantly high in regional lymph node metastasis than those without metastasis in papillary thyroid carcinoma. 4) The expression of E-cadherin demonstrated less often among papillary carcinomas with lymph node metastasis than in those without metastasis in papillary thyroid carcinoma. In conclusion, it is suggested that VEGF and E-cadherin will be useful for the diagnosis of thyroid carcinoma and serves as a biological marker for thyroid carcinoma lymph node metastasis.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3015-3023
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• 2012

The mitochondrial antioxidant protein manganese superoxide dismutase (MnSOD) may represent a new type of tumor suppressor protein. Overexpression of the cDNA of this gene by plasmid or recombinant lentiviral transfection in various types of cancer leads to growth suppression both in vitro and in vivo. We previously determined that changes in MnSOD expression had bidirectional effects on adriamycin (ADR) when combined with nitric oxide (NO). Radiation induces free radicals in a manner similar to ADR, so we speculated that MnSOD combined with NO would also have a bidirectional effect on cellular radiosensitivity. To examine this hypothesis, TE-1 human esophageal squamous carcinoma cells were stably transfected using lipofectamine with a pLenti6-DEST plasmid containing human MnSOD cDNA at moderate to high overexpression levels or with no MnSOD insert. Blastidicin-resistant colonies were isolated, grown, and maintained in culture. We found that moderate overexpression of MnSOD decreased growth rates, plating efficiency, and increased apoptosis. However, high overexpression increased growth rates, plating efficiency, and decreased apoptosis. When combined with NO, moderate overexpression of MnSOD increased the radiosensitivity of esophageal cancer cells, whereas high MnSOD overexpression had the opposite effect. This finding suggests a potential new method to kill certain radioresistant tumors and to provide radioresistance to normal cells.

• BMB Reports
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• v.41 no.2
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• pp.164-169
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• 2008

The tumor suppressor gene p53 regulates apoptotic cell death and the cell cycle. In this study, we investigated the role of p53 in nitric oxide (NO)-induced apoptosis in vascular smooth muscle cells (VSMCs). We found that the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) increased apoptotic cell death in p53-deficient VSMCs compared with wild-type cells. The heme oxygen-ase (HO) inhibitor tin protoporphyrin IX reduced the resistance of wild-type VSMCs to SNAP-induced cell death. SNAP promoted HO-1 expression in both cell types. HO-2 protein was increased only in wild-type VSMCs following SNAP treatment; however, similar levels of HO-2 mRNA were detected in both cell types. SNAP significantly increased the levels of non-heme-iron and dinitrosyl iron-sulfur clusters in wild-type VSMCs compared with p53-deficient VSMCs. Moreover, pretreatment with FeSO4 and the carbon monoxide donor CORM-2, but not biliverdin, significantly protected p53-deficient cells from SNAP-induced cell death compared with normal cells. These results suggest that wild-type VSMCs are more resistant to NO-mediated apoptosis than p53-deficient VSMCs through p53-dependent up-regulation of HO-2.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3293-3299
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• 2015

Background: Arm protein lost in epithelial cancers, on chromosome X (ALEX) is a novel subgroup within the armadillo (ARM) family, which has one or two ARM repeat domains as opposed to more than six-thirteen repeats in the classical Armadillo family members. Materials and Methods: In the study, we explore the biological functions of ALEX1 in breast cancer cells. Overexpression of ALEX1 and silencing of ALEX1 were performed with SK-BR3 and MCF-7 cell lines. Cell proliferation and colony formation assays, along with flow cytometry, were carried out to evaluate the roles of ALEX1. Results: ALEX1 overexpression in SK-BR3 breast cancer cells inhibited proliferation and induced apoptosis. Furthermore, depletion of ALEX1 in MCF-7 breast cancer cells increased proliferation and inhibited apoptosis. Additional analyses demonstrated that the overexpression of ALEX1 activated the intrinsic apoptosis cascades through up-regulating the expression of Bax, cytosol cytochrome c, active caspase-9 and active caspase-3 and down-regulating the levels of Bcl-2 and mitochondria cytochrome c. Simultaneouly, silencing of ALEX1 inhibited intrinsic apoptosis cascades through down-regulating the expression of Bax, cytosol cytochrome c, active caspase-9, and active caspase-3 and up-regulating the level of Bcl-2 and mitochondria cytochrome c. Conclusions: Our data suggest that ALEX1 as a crucial tumor suppressor gene has been involved in cell proliferation and apoptosis in breast cancer, which may serve as a novel candidate therapeutic target.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1833-1836
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• 2012

Objective: Promoter methylation, which can be regulated by MTHFR activity, is associated with silencing of genes. In this study we evaluated the methylation status (type) of the BRCA2 promoter in ovarian cancer patients carrying different genotypes of the MTHFR gene (A or C polymorphisms at position 1298). Methods: The methylation type of the BRCA2 promoter was evaluated using bisulfate-modified DNA in methylation-specific PCR and the MTHFRa1278c polymorphism was assessed by PCR-RFLP. Results: Analysis of the BRCA2 promoter methylation type of cases showed that 7 out of 60 cases (11.7%) were methylated while the remaining 53 (88.3%) were unmethylated. In methylated cases, one out of the 7 cases had a CC genotype and the remaining 6 methylated cases had an AC genotype. The AA genotype was absent. In unmethylated cases, 34, 18, and one out of these had AC, AA and CC genotype, respectively. Conclusion: There was no significant relationship between the methylation types of the BRCA2 promoter in different genotypes of MTHFRa1298c polymorphism in ovarian cancer; p=0.255. There was no significant relation between the methylation types of the BRCA2 promoter in different genotypes of the MTHFRa1298c polymorphism in ovarian cancer.

• Journal of Microbiology and Biotechnology
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• v.19 no.11
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• pp.1482-1489
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• 2009

In this study, we investigated the anti-proliferative effect of polysaccharides from Salicornia herbacea on HT-29 human colon cancer cells. Crude polysaccharides from S. herbacea (CS) were prepared by extraction with hot steam water, and fine polysaccharides from S. herbacea (PS) were obtained through further size exclusion chromatography. The anti-proliferative effect of CS and PS were measured using the MTS assay, apoptosis analysis, cell cycle analysis, and RT-PCR. HT-29 cells were treated with CS or PS at different dosages (0.5, 1, 2, 4 mg $ml^{-1}$) for 24 or 48 h. CS and PS inhibited proliferation and stimulated apoptosis of cells in a dose-dependent manner. Flow cytometric analysis after Annexin V-FITC and PI staining revealed that treatment with CS or PS increased total apoptotic death of cells to 24.99% or 91.59%, respectively, in comparison with the control (13.51 %). PS increased early apoptotic death substantially - up to 12 times more than the control. Treatment with CS or PS resulted in a concentration-dependent increase of the G2/M cell population of the cell cycle as determined by flow cytometry. G2/M arrest was induced significantly with the highest concentration (4 mg $ml^{-1}$) of PS. RT-PCR was performed to study the correlation between G2/M arrest and transcription of cell cycle control genes. The anti-proliferative activity of CS and PS was accompanied by inhibition of cyclin B1, and Cdc 2 mRNA. Moreover, both CS and PS induced expression of the p53 tumor suppressor gene and the Cdk inhibitor p21. These results suggest that polysaccharides from S. herbacea have anti-cancer activity in human colon cancer cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.3
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• pp.722-728
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• 2005

The DNA topoismerase I inhibitor ${\beta}-lapachone$, the product of a lapacho tree (Tabebuia avellanedae) from South America, activates a novel apoptotic response in a number of cell lines. In the present report, we investigated the effects of ${\beta}-lapachone$ on the growth of human lung in human non-small-cell-lung-cancer A549 cells. Upon treatment with ${\beta}-lapachone$, a concentration-dependent inhibition of cell viability and cell proliferation was observed as measured by hemocytometer counts and MTT assay. The ${\beta}-lapachone-treated$ cells developed many of the hallmark features of apoptosis, including membrane shrinking, condensation of chromatin and DNA fragmentation. These apoptotic effects of ${\beta}-lapachone$ in A549 cells were associated with a marked induction of pro-apoptotic Bax expression, however the levels of anti-apoptotic Bcl-2 expression were decreased in a dose-dependent manner. Accordingly, elevated amount of cyclin-dependent kinase inhibitor p21 expression accompanied by up-regulation of tumor suppressor p53 was observed. By RT-PCR analyses, decrease in gene expression level of telomerase reverse transcriptase and telomeric repeat binding factor were also observed. Thus, these findings suggest that ${\beta}-lapachone$ may be a potential anti-cancer therapeutics for the control of human lung cancer cell model.

• Experimental and Molecular Medicine
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• v.50 no.11
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• pp.10.1-10.11
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• 2018

Although early studies suggested that bladder cancer (BCa) is more prevalent in men than in women, muscle-invasive rates are higher in women than in men, suggesting that sex hormones might play important roles in different stages of BCa progression. In this work, we found that estrogen receptor beta ($ER{\beta}$) could increase BCa cell proliferation and invasion via alteration of miR-92a-mediated DAB2IP (DOC-2/DAB2 interacting protein) signals and that blocking miR-92a expression with an inhibitor could partially reverse $ER{\beta}$-enhanced BCa cell growth and invasion. Further mechanism dissection found that $ER{\beta}$ could increase miR-92a expression at the transcriptional level via binding to the estrogen-response-element (ERE) on the 5' promoter region of its host gene C13orf25. The $ER{\beta}$ up-regulated miR-92a could decrease DAB2IP tumor suppressor expression via binding to the miR-92a binding site located on the DAB2IP 3' UTR. Preclinical studies using an in vivo mouse model also confirmed that targeting this newly identified $ER{\beta}$/miR-92a/DAB2IP signal pathway with small molecules could suppress BCa progression. Together, these results might aid in the development of new therapies via targeting of this $ER{\beta}$-mediated signal pathway to better suppress BCa progression.

• Journal of Acupuncture Research
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• v.21 no.2
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• pp.41-55
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• 2004

Objective : To investigate the possible molecular mechanism (s) of melittin as a candidate of anti-cancer drug, we examined the effects of the compound on the growth of human lung carcinoma cell line A549. Methods : Growth inhibitory study, flow cytometry analysis, SDS-polyacrylamide gel electrophoresis and Western blot analysis, RT-PCR and in vitro caspases activity assay were performed. Results : Melittin treatment declined the cell viability of A549 cells in a concentration-dependent manner, which was associated with induction of apoptotic cell death. Melittin treatment down-regulated the levels of Bcl-XS/L mRNA and protein expression of A549 cells, an anti-apoptotic gene, however, the those of Bax, a pro-apoptotic gene, were up-regulated. Melittin induced the proteolytic cleavage and activation of caspase-3 and caspase-9 protease in a dose-dependent manner without alteration of inhibitor of apoptosis proteins family and Akt expression. Western blot analysis and RT-PCR data revealed that the levels of tumor suppressor p53 and cyclin-dependent kinase inhibitor p21 were also remained unchanged. Conclusions : Taken together, these findings suggest that melittin-induced inhibition of human lung cancer cell growth is associated with the induction of apoptotic cell death via regulation of several major growth regulatory gene products, and melittin may have therapeutic potential in human lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.sup3
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• pp.219-224
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• 2016

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver making up more than 80 percent of cases. It is known to be the sixth most prevalent cancer and the third most frequent cause of cancer related death worldwide. Epigenetic regulation constitutes an important mechanism by which dietary components can selectively activate or inactivate target gene expression. The miR-34 family members including mir-34a, mir-34b and mir-34c are tumor suppressor micro RNAs, which are expressed in the majority of normal tissues. Several studies have indicated silencing of miR-34 expression via DNA methylation in multiple types of cancers. Bioactive nutrients like curcumin (Cur) have excellent anticarcinogenic activity and minimal toxic manifestations in biological systems. This compound has recently been determined to induce epigenetic changes. However, Cur is lipophilic and has a poor systemic bioavailability and poor absorption. Its bioavailability is increased through employing dendrosome nanoparticles. The aim of the current study was to investigate the effect of dendrosomal nanocurcumin (DNC) on expression of mir-34 family members in two HCC cell lines, HepG2 and Huh7. We performed the MTT assay to evaluate DNC and dendrosome effects on cell viability. The ability of DNC to alter expression of the mir-34 family and DNA methyltransferases (DNMT1, DNMT3A and 3B) was evaluated using semi-quantitative and quantitative PCR. We observed the entrance of DNC into HepG2 and Huh7 cells. Gene expression assays indicated that DNC treatment upregulated mir34a, mir34b and mir34c expression (P<0.05) as well as downregulated DNMT1, DNMT3A and DNMT3B expression (P<0.05) in both HepG2 and Huh7 cell lines. DNC also reduced viability of Huh7 and HepG2 cells through restoration of miR-34s expression. We showed that DNC could awaken the epigenetically silenced miR-34 family by downregulation of DNMTs. Our findings suggest that DNC has potential in epigenetic therapy of HCC.