• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.165-171
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• 2013

The aim of the present study was to analyze the expression of FHIT and WWOX in nasopharyngeal carcinoma (NPC) and correlations with clinical pathologic features. mRNA expression of the FHIT and WWOX was assessed by real-time fluorescent relatively quantitative PCR in 61 NPC tissues and 45 non-cancerous nasopharyngeal tissues. As a result, mRNA expression levels of both FHIT and WWOX were significantly lower in NPC patients than in control samples (P=0.049 and 0.045, respectively). Moreover, the mRNA expression of both had an inverse relation with larger invasive range (P=0.035 and 0.048, respectively), poor histologic differentiation (P=0.012 and 0.016) and advanced clinical stage (P=0.026 and 0.038). Consistency was found between expression of FHIT and WWOX in the same NPC tissues (r=0.681, P=0.00). In conclusion, synergy between FHIT and WWOX may exist in the development of NPC so that the two factors may be considered as important genetic markers. Detecting the expression of FHIT and WWOX should provide clinically significant information relevatn to tumor diagnosis, progression and treatment modalities for NPC.

• Bulletin of the Korean Chemical Society
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• v.32 no.8
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• pp.2817-2819
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• 2011

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6429-6433
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• 2012

To explore a possible new treatment for human ovarian cancer, we studied the effects of sodium valproate on the growth of the HO8910 human cell line. HO8910 cells were cultured in vitro and treated with different concentrations of sodium valproate. Cell proliferation, cell cycling, and apoptosis were measured by flow cytometry, cell morphology under a microscope, and expression levels of WWOX and P27 by Western blotting and RT-PCR. Tumor xenografts were established to determine in vivo effects of sodium valproate. Our results showed that cell proliferation was decreased with increasing concentration of sodium valproate, with features of cytoplasmic retraction and floating cells. Moreover, cell cycle analysis revealed a higher apoptosis rate and $G_0/G_1$ phase in the sodium valproate experimental group than in the control group. In addition, protein expression levels of WWOX and P27 were elevated. Importantly, sodium valproate decreased in vivo xenograft tumor burden and up-regulated WWOX and P27 expression in nude mice. In conclusion, sodium valproate might play a role in inhibition and control of ovarian cancer cell line HO8910 by inhibiting cell proliferation, interfering with the cell cycle and promoting apoptosis, so that it may be effective in the clinical treatment of ovarian cancer.

• Bulletin of the Korean Chemical Society
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• v.33 no.8
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• pp.2756-2758
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• 2012

• Journal of the Society of Cosmetic Scientists of Korea
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• v.40 no.4
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• pp.403-412
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• 2014

To develop an effective skin whitening agent for cosmetics, we isolated cucurbitacin B from Cucumis sativus L. which has been used as traditional skin lighting regimen by the bioactivity-guided fractionation, and investigated the inhibitory effects of cucurbitacin B on melanogenesis. At a non-cytotoxic concentration, cucurbitacin B reduced melanin contents of B16F1 melanoma cells in a dose-dependent manner. Cucurbitacin B did not directly inhibit mushroom tyrosinase activity, but it inhibited intracellular tyrosinase activity in a dose-dependent manner. Its inhibitory mechanism on melanin biosynthesis was further assessed, and we found that cucurbitacin B significantly decreased the protein level of tyrosinase, a major melanogenic enzymes and MITF, a master transcriptional factor of melanogenesis. In addition, cucurbitacin B increased the expression of WW domain-containing oxidoreductase (WWOX) which is known to function as tumor repressor and inhibits $Wnt/{\beta}$-catenin pathway. Collectively, these results suggest that cucuritacin B from C. sativus could be used as an active ingredient for skin whitening.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5799-5804
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• 2012

Family with sequence similarity 189, member B (FAM189B), alias COTE1, a putative oncogene selected by microarray, for the first time was here found to be significantly up-regulated in hepatocellular carcinoma (HCC) specimens and HCC cell lines. mRNA expression of COTE1 in HCC samples and cell lines was detected by reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR, while protein expression of COTE1 in HCC tissues was assessed by immunohistochemistry. In addition, invasion of HCC cells was observed after overexpressing or silencing COTE1. In the total of 48 paired HCC specimens, compared with the adjacent non-cancer tissues, the expression of COTE1 was up-regulated in 31 (p<0.01). In HCC cell lines, COTE1 expression was significantly higher than in normal human adult liver (p<0.01). Overexpression of COTE1 enhanced HCC-derived LM6 and MHCC-L cellular invasion in vitro. In contrast, COTE1 knockdown via RNAi markedly suppressed these phenotypes, as documented in LM3 and MHCC-H HCC cells. Mechanistic analyses indicated that COTE1 could physically associate with WW domain oxidoreductase (WWOX), a tumor suppressor. COTE1 may be closely correlated with invasion of hepatocellular carcinoma (HCC) cells and thus may serve as an effective target for gene therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.9
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• pp.3973-3980
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• 2014

Prostate adenocarcinoma is one of the leading causes of cancer related mortality in men but still limited knowledge is available about its associated functional SNPs including rs1042522 (Pro72Arg). The present study was undertaken to explore the association of this SNP with susceptibility to prostate adenocarcinoma along with its structural and functional impacts in the Pakistani population in a case-control study. Three-dimensional structure of human TP53 with Pro72Arg polymorphism was predicted through homology modeling, refined and validated for detailed structure-based assessment. We also carried out a HuGE review of the previous available data for this polymorphism. Different genetic models were used to evaluate the genotypes association with the increased risk of PCa (Allelic contrast: OR=0.0.34, 95%CI 0.24-0.50, p=0.000; GG vs CC: OR=0.17, 95%CI 0.08-0.38, p=0.000; Homozygous: OR=0.08, 95%CI 0.04-0.15, p=0.000; GC vs CC: OR=2.14, 95%CI 1.01-4.51, p=0.046; Recessive model: OR=0.10, 95%CI 0.05-0.18, p=0.000; Log Additive: OR=3.54, 95%CI 2.13-5.89, p=0.000) except the Dominant model (OR=0.77, 95%CI 0.39-1.52, p=0.46). Structure and functional analysis revealed that the SNP in the proline rich domain is responsible for interaction with HRMT1L2 and WWOX. In conclusion, it was observed that the Arg coding G allele is highly associated with increased risk of prostate adenocarcinoma in the Pakistani population (p=0.000).

• Molecules and Cells
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• v.45 no.12
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• pp.911-922
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• 2022

A structural protein of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), nucleocapsid (N) protein is phosphorylated by glycogen synthase kinase (GSK)-3 on the serine/arginine (SR) rich motif located in disordered regions. Although phosphorylation by GSK-3β constitutes a critical event for viral replication, the molecular mechanism underlying N phosphorylation is not well understood. In this study, we found the putative alpha-helix L/FxxxL/AxxRL motif known as the GSK-3 interacting domain (GID), found in many endogenous GSK-3β binding proteins, such as Axins, FRATs, WWOX, and GSKIP. Indeed, N interacts with GSK-3β similarly to Axin, and Leu to Glu substitution of the GID abolished the interaction, with loss of N phosphorylation. The N phosphorylation is also required for its structural loading in a virus-like particle (VLP). Compared to other coronaviruses, N of Sarbecovirus lineage including bat RaTG13 harbors a CDK1-primed phosphorylation site and Gly-rich linker for enhanced phosphorylation by GSK-3β. Furthermore, we found that the S202R mutant found in Delta and R203K/G204R mutant found in the Omicron variant allow increased abundance and hyper-phosphorylation of N. Our observations suggest that GID and mutations for increased phosphorylation in N may have contributed to the evolution of variants.