Most disease single nucleotide polymorphisms (SNPs) are regulatory and approximately half of heritability is occupied by the top 1% of genes, with the gene-level structure varying with the number of ...variants associated with the most common alleles. Cancer occurrence and progression are significantly affected by Claspin (CLSPN) gene polymorphism present in the population, which alters the expression, function, and regulation of the gene. CLSPN genotypes are associated with oral cancer, but the literature on this association is limited. As a result, the goal of this study is to investigate the correlation between CLSPN genotypes and oral cancers' development. This study will explore the presence of four CLSPN SNPs including rs12058760, rs16822339, rs535638 and rs7520495 gene polymorphisms, and analyze the expression of these genes in 304 cancer-free controls and 402 oral squamous cell carcinoma (OSCC) cases. Attempts have been made to obtain insight into the role of CLSPN gene polymorphisms in oral cancer through the analysis of this study. We demonstrated that the OSCC risk of individuals with four CLSPN SNPs relative to the wild type did not differ significantly from that of the wild type when the polymorphisms are analyzed according to individual habits. We further studied the mechanism by which CLSPN polymorphisms affect the progression of clinicopathological features in OSCC patients. The results of the degree of cell differentiation showed that compared with patients of rs7520495 SNP carrying the CC genotype, the incidence of poor cell differentiation in patients carrying the CC + GG genotype was higher (AOR: 1.998-fold; 95% CI, 1.127-3.545; p = 0.018). In particular, patients with the G genotype of rs7520495 had increased poor cell differentiation compared with patients with the C genotype (AOR: 4.736-fold; 95% CI, 1.306-17.178; p = 0.018), especially in the drinking group. On the basis of our analysis of the Cancer Genome Atlas dataset, we found that higher CLSPN levels were associated with poorer cell differentiation in oral cancers. In this study, we provide the first evidence showing that CLSPN SNPs contribute to oral cancer. Whether or not rs7520495 can be used as a confirmatory factor in the future is uncertain, but it seems likely that it can be used as an important factor in predicting recurrence, response to treatment and medication toxicity to patients with oral cancer.
Head and neck squamous cell carcinoma (HNSCC) are associated with recurrence, distant metastasis, and poor overall survival. This highlights the need for identifying potential therapeutics with ...minimal side-effects. The present study was designed to investigate the anticancer effects of picrasidine J, a dimeric β-carboline-type alkaloid isolated from the southern Asian plant Picrasma quassioides. The results showed that picrasidine J significantly inhibits HNSCC cell motility, migration, and invasion. Specifically, picrasidine J inhibited the EMT process by upregulating E-cadherin and ZO-1 and downregulating beta-catenin and Snail. Moreover, picrasidine J reduced the expression of the serine protease KLK-10. At the signaling level, the compound reduced the phosphorylation of ERK. All these factors collectively facilitated the inhibition of HNSCC metastasis with picrasidine J. Taken together, the study identifies picrasidine J as a potential anticancer compound of plant origin that might be used clinically to prevent the distant metastasis and progression of HNSCC.
Oral cancer ranks fourth among malignancies among Taiwanese men and is the eighth most common cancer among men worldwide in terms of general diagnosis. The purpose of the current study was to ...investigate how low-density lipoprotein receptor-related protein 1B (LDL receptor related protein 1B; LRP1B) gene polymorphisms affect oral squamous cell carcinoma (OSCC) risk and progression in individuals with diabetes mellitus (DM). Three LRP1B single-nucleotide polymorphisms (SNPs), including rs10496915, rs431809, and rs6742944, were evaluated in 311 OSCC cases and 300 controls. Between the case and control groups, we found no evidence of a significant correlation between the risk of OSCC and any of the three specific SNPs. Nevertheless, in evaluating the clinicopathological criteria, individuals with DM who possess a minimum of one minor allele of rs10496915 (AC + CC;
= 0.046) were significantly associated with tumor size compared with those with homozygous major alleles (AA). Similarly, compared to genotypes homologous for the main allele (GG), rs6742944 genotypes (GA + AA;
= 0.010) were more likely to develop lymph node metastases. The tongue and the rs6742944 genotypes (GA + AA) exhibited higher rates of advanced clinical stages (
= 0.024) and lymph node metastases (
= 0.007) when compared to homozygous alleles (GG). LRP1B genetic polymorphisms appear to be prognostic and diagnostic markers for OSCC and DM, as well as contributing to genetic profiling research for personalized medicine.
Head and neck squamous cell carcinoma (HNSCC) is one of the most common histological types of head and neck cancer. Epiberberine is a potent antitumour agent for several types of cancer. This study ...is aimed at investigating the regulatory and molecular mechanism of epiberberine on HNSSC cell metastasis. The results showed that epiberberine inhibited the motility of Ca9‐22 and FaDu cell lines at nontoxicity doses. Moreover, the epithelial‐mesenchymal transition (EMT)‐related proteins, vimentin, snail and slug, were found suppressing after epiberberine treatments. In addition, the JNK signalling cascade and the metalloproteinase 13 (MMP‐13) expression were also found downregulated by epiberberine. In conclusion, the present study demonstrates that epiberberine suppresses cell migration and invasion by regulating the JNK pathway and MMP‐13. These results suggest that epiberberine could be a potential antimetastatic agent in HNSCC cells.
Oral squamous cell carcinoma (OSCC), which accounts for 90% of all oral cancers, has become a public health crisis worldwide. despite advances in therapeutic interventions, the prognosis remains poor ...for advanced‐stage OSCC. In this study, we investigate the anticancer activity and the mode of action of hellebrigenin in human OSCC. The findings demonstrated that hellebrigenin exerted cytotoxic effects in OSCC cells through cell cycle arrest at the G2/M phase and downregulation of cell cycle‐related proteins (cyclins A2, B1 and D3, Cdc2, CDK4 and CDK6). Moreover, hellebrigenin caused activation of PARP and caspase 3, 8 and 9, followed by downregulation of antiapoptotic proteins (Bcl‐2 and Bcl‐xL) and upregulation of pro‐apoptotic proteins (Bax and Bak). The hellebrigenin treatment also increased Fas, DR5, DcR2 and DcR3 expressions in oral cancer cells, indicating the compound causes oral cancer cell apoptosis through both intrinsic and extrinsic pathways. Regarding upstream signalling, hellebrigenin was found to reduce the phosphorylation of ERK, p38, and JNK, indicating that hellebrigenin triggers caspase‐mediated apoptosis by downregulating MAPK signalling pathway. Finally, the human apoptosis array findings revealed that hellebrigenin specifically suppressed the expression of XIAP to execute its pro‐apoptotic activities. Taken together, the study suggests that hellebrigenin can act as a potent anticancer compound in human OSCC.
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Although cisplatin‐based chemotherapy is commonly used in HNSCC, frequent development of cisplatin resistance ...is a potential cause of poor HNSCC prognosis. In the present study, we investigated the anticancer efficacy of a major paclitaxel metabolite namely 7‐Epitaxol in cisplatin‐resistant HNSCC. The findings revealed that 7‐Epitaxol exerts cytotoxic effects in cisplatin‐resistant HNSCC cell lines by inducing cell cycle arrest and intrinsic and extrinsic apoptotic pathways. Specifically, 7‐Epitaxol increased Fas, TNF‐R1, DR5, DcR3 and DcR2 expressions, reduced Bcl‐2 and Bcl‐XL (anti‐apoptotic proteins) expressions, and increased Bid and Bim L/S (pre‐apoptotic proteins) expressions, leading to activation of caspase‐mediated cancer cell apoptosis. At the upstream cell signalling level, 7‐Epitaxol reduced the phosphorylation of AKT, ERK1/2 and p38 to trigger apoptosis. In vivo results showed that animals treated with 7‐Epitaxol show antitumor growth compared to control animals. Taken together, the study demonstrates the potential anticancer efficacy of 7‐Epitaxol in inducing apoptosis of cisplatin‐resistant HNSCC cells through the suppression of AKT and MAPK signalling pathways.
Summary
Emerging azole resistance in Aspergillus fumigatus poses a serious threat to human health. This nationwide surveillance study investigated the prevalence and molecular characteristics of ...azole‐resistant A. fumigatus environmental isolates in Taiwan, an island country with increasing use of azole fungicides. Of the 2760 air and soil samples screened from 2014 to 2016, 451 A. fumigatus isolates were recovered from 266 samples and 34 isolates from 29 samples displayed resistance to medical azoles (itraconazole, voriconazole or posaconazole). The resistance prevalence was 10.9% and 7.5% in A. fumigatus‐positive samples and isolates respectively. Most (29, 85.3%) azole‐resistant isolates harboured TR34/L98H mutations, which were widely distributed, clustered genetically with clinical isolates, and had growth rates that were similar to those of the wild‐type isolates. Microsatellite genotyping revealed both the global spread of the TR34/L98H isolates and the occurrence of TR34/L98H/S297T/F495I isolates belonging to local microsatellite genotypes. AfuMDR3 and atrF, two efflux transporter genes, were constitutively upregulated in two individual resistant isolates without cyp51A mutations, highlighting their potential roles in azole resistance. These results emphasize the need for periodic environmental surveillance at the molecular level in regions in which azole fungicides are applied, and agricultural fungicide management strategies that generate less selective pressure should be investigated.
The prevalence of oral squamous cell carcinoma (OSCC) is increasing worldwide mainly due to poor oral hygiene and unrestricted lifestyle. Advanced‐stage OSCC is associated with poor prognosis and a ...5‐year survival rate of only 30%–50%. The present study was designed to investigate the anticancer effect and mode of action of Glycyrrhiza‐derived semilicoisoflavone B (SFB) in 5‐fluorourasil (5FU)‐resistant human OSCC cell lines. The study findings revealed that SFB significantly reduces OSCC cell viability and colony formation ability by arresting cell cycle at the G2/M and S phases and reducing the expressions of key cell cycle regulators including cyclin A, cyclin B, CDC2, and CDK2. The compound caused a significant induction in the percentage of nuclear condensation and apoptotic cells in OSCC. Regarding pro‐apoptotic mode of action, SFB was found to increase Fas‐associated death domain and death receptor 5 expressions and reduce decoy receptor 2 expression, indicating involvement of extrinsic pathway. Moreover, SFB was found to increase pro‐apoptotic Bim expression and reduce anti‐apoptotic Bcl‐2 and Bcl‐xL expressions, indicating involvement of intrinsic pathway. Moreover, SFB‐mediated induction in cleaved caspases 3, 8, and 9 and cleaved poly(ADP‐ribose) polymerase confirmed the induction of caspase‐mediated apoptotic pathways. Regarding upstream signaling pathway, SFB was found to reduce extracellular signal regulated kinase 1/2 (ERK) phosphorylation to execute its pro‐apoptotic activity. The Human Apoptotic Array findings revealed that SFB suppresses claspin expression, which in turn caused reduced phosphorylation of ATR, checkpoint kinase 1 (Chk1), Wee1, and CDC25C, indicating disruption of ATR‐Chk1 signaling pathway by SFB. Taken together, these findings indicate that SFB acts as a potent anticancer compound against 5FU‐resistant OSCC by modulating mitogen‐activated protein kinase (MAPK) and ATR‐Chk1 signaling pathways.
Nasopharyngeal carcinoma (NPC) is an unnoticeable malignant tumor with a high potential of lymphatic metastasis, and its prevalence is high in Asia. Ionizing radiation is the mainstay of treatment ...for patients with NPC without metastasis. However, patients with metastatic lesions require advanced treatments such as chemotherapy. The present study investigated the apoptotic effect of luteolin‐7‐O‐glucoside on NPC cells and elucidated its underlying signaling mechanisms. The results revealed that luteolin‐7‐O‐glucoside significantly reduced the proliferation of NPC cell lines (NPC‐039 and NPC‐BM). Flow cytometry and morphological analysis results demonstrated that luteolin‐7‐O‐glucoside treatment induced S and G2/M cell cycle arrest, chromatin condensation, and apoptosis. In addition, mitochondrial membrane potential was observed to be depolarized with an increasing concentration of luteolin‐7‐O‐glucoside. Proteins involved in the extrinsic and intrinsic pathways of apoptosis, such as death receptor, caspase‐3, caspase‐8, caspase‐9, and Bcl‐2 family proteins (Bax, t‐Bid, Bcl‐2, and Bcl‐xL), were downregulated and upregulated after treatment with luteolin‐7‐O‐glucoside, respectively. Moreover, the addition of a PI3K/AKT inhibitor enhanced the activation of poly‐ADP‐ribose‐polymerase (PARP) and attenuated cell viability, indicating that luteolin‐7‐O‐glucoside induced apoptosis in NPC cells through the AKT signaling pathway. These results indicated that the apoptosis of NPC cells modulated by luteolin‐7‐O‐glucoside may be preceded by mitochondrial depolarization, cell cycle arrest, extrinsic and intrinsic apoptosis pathway activation, and AKT signaling modulation. Thus, luteolin‐7‐O‐glucoside can be a promising anticancer agent against human NPC.
Platyphyllenone is a type of diarylheptanoid that exhibits anti-inflammatory and chemoprotective effects. However, its effect on oral cancer remains unclear. In this study, we investigated whether ...platyphyllenone can promote apoptosis and autophagy in SCC-9 and SCC-47 cells. We found that it dose-dependently promoted the cleavage of PARP; caspase-3, -8, and -9 protein expression; and also led to cell cycle arrest at the G2/M phase. Platyphyllenone up-regulated LC3-II and p62 protein expression in both SCC-9 and SCC-47 cell lines, implying that it can induce autophagy. Furthermore, the results demonstrated that platyphyllenone significantly decreased p-AKT and increased p-JNK1/2 mitogen-activated protein kinase (MAPK) signaling pathway in a dose-dependent manner. The specific inhibitors of p-JNK1/2 also reduced platyphyllenone-induced cleavage of PARP, caspase-3, and caspase -8, LC3-II and p62 protein expression. These findings are the first to demonstrate that platyphyllenone can induce both autophagy and apoptosis in oral cancers, and it is expected to provide a therapeutic option as a chemopreventive agent against oral cancer proliferation.
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