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1.  Antiproliferative Effects of Methanolic Extracts of Cryptocarya concinna Hance Roots on Oral Cancer Ca9-22 and CAL 27 Cell Lines Involving Apoptosis, ROS Induction, and Mitochondrial Depolarization 
The Scientific World Journal  2014;2014:180462.
Cryptocarya-derived natural products were reported to have several biological effects such as the antiproliferation of some cancers. The possible antioral cancer effect of Cryptocarya-derived substances was little addressed as yet. In this study, we firstly used the methanolic extracts of C. concinna Hance roots (MECCrt) to evaluate its potential function in antioral cancer bioactivity. We found that MECCrt significantly reduced cell viability of two oral cancer Ca9-22 and CAL 27 cell lines in dose-responsive manners (P < 0.01). The percentages of sub-G1 phase and annexin V-positive of MECCrt-treated Ca9-22 and CAL 27 cell lines significantly accumulated (P < 0.01) in a dose-responsive manner as evidenced by flow cytometry. These apoptotic effects were associated with the findings that intracellular ROS generation was induced in MECCrt-treated Ca9-22 and CAL 27 cell lines in dose-responsive and time-dependent manners (P < 0.01). In a dose-responsive manner, MECCrt also significantly reduced the mitochondrial membrane potential in these two cell lines (P < 0.01–0.05). In conclusion, we demonstrated that MECCrt may have antiproliferative potential against oral cancer cells involving apoptosis, ROS generation, and mitochondria membrane depolarization.
doi:10.1155/2014/180462
PMCID: PMC4213999  PMID: 25379520
2.  Expression of a Splice Variant of CYP26B1 in Betel Quid-Related Oral Cancer 
The Scientific World Journal  2014;2014:810561.
Betel quid (BQ) is a psychostimulant, an addictive substance, and a group 1 carcinogen that exhibits the potential to induce adverse health effects. Approximately, 600 million users chew a variety of BQ. Areca nut (AN) is a necessary ingredient in BQ products. Arecoline is the primary alkaloid in the AN and can be metabolized through the cytochrome P450 (CYP) superfamily by inducing reactive oxygen species (ROS) production. Full-length CYP26B1 is related to the development of oral pharyngeal cancers. We investigated whether a splice variant of CYP26B1 is associated with the occurrence of ROS related oral and pharyngeal cancer. Cytotoxicity assays were used to measure the effects of arecoline on cell viability in a dose-dependent manner. In vitro and in vivo studies were conducted to evaluate the expression of the CYP26B1 splice variant. The CYP26B1 splice variant exhibited lower expression than did full-length CYP26B1 in the human gingival fibroblast-1 and Ca9-22 cell models. Increased expression of the CYP26B1 splice variant was observed in human oral cancer tissue compared with adjacent normal tissue, and increased expression was observed in patients at a late tumor stage. Our results suggested that the CYP26B1 splice variant is associated with the occurrence of BQ-related oral cancer.
doi:10.1155/2014/810561
PMCID: PMC4119653  PMID: 25114974
3.  The antiproliferative effect of C2-ceramide on lung cancer cells through apoptosis by inhibiting Akt and NFκB 
The anticancer effects of ceramide have been reported in many types of cancers but less in lung cancer. In this study, we used C2-ceramide to further investigate its possible anticancer effects and mechanisms on non-small cell lung cancer (NSCLC) H1299 cells. The result of cell proliferation in terms of trypan blue assay showed high dose of C2-ceramide inhibited cell survival after 24 h treatment. The flow cytometry-based assays indicated the effect of apoptosis, chromatin condensation, and G1 arrest in terms of Annexin V/propidium iodide (PI), DAPI, and PI stainings, respectively. Moreover, the decreased protein level of p-Akt, p-NFκB, survivin and cyclin A2 were detected by Western blot assay. Taken together, these results indicated the antiproliferative effect of C2-ceramide is majorly responsible for cell apoptosis in lung cancer H1299 cells.
doi:10.1186/1475-2867-14-1
PMCID: PMC3893380  PMID: 24393431
Lung cancer; Apoptosis; NSCLC; Ceramides; p-Akt; p-NFκB; survivin; cyclin A2
4.  Different Genetic Associations of the IgE Production among Fetus, Infancy and Childhood 
PLoS ONE  2013;8(8):e70362.
Elevation of serum IgE levels has long been associated with allergic diseases. Many genes have been linked to IgE production, but few have been linked to the developmental aspects of genetic association with IgE production. To clarify developmental genetic association, we investigated what genes and gene-gene interactions affect IgE levels among fetus, infancy and childhood in Taiwan individuals. A birth cohort of 571 children with completion of IgE measurements from newborn to 1.5, 3, and 6 years of age was subject to genetic association analysis on the 384-customized SNPs of 159 allergy candidate genes. Fifty-three SNPs in 37 genes on innate and adaptive immunity, and stress and response were associated with IgE production. Polymorphisms of the IL13, and the HLA-DPA1 and HLA-DQA1 were, respectively, the most significantly associated with the IgE production at newborn and 6 years of age. Analyses of gene-gene interactions indentified that the combination of NPSR1, rs324981 TT with FGF1, rs2282797 CC had the highest risk (85.7%) of IgE elevation at 1.5 years of age (P = 1.46×10−4). The combination of IL13, CYFIP2 and PDE2A was significantly associated with IgE elevation at 3 years of age (P = 5.98×10−7), and the combination of CLEC2D, COLEC11 and CCL2 was significantly associated with IgE elevation at 6 years of age (P = 6.65×10−7). Our study showed that the genetic association profiles of the IgE production among fetus, infancy and childhood are different. Genetic markers for early prediction and prevention of allergic sensitization may rely on age-based genetic association profiles.
doi:10.1371/journal.pone.0070362
PMCID: PMC3731352  PMID: 23936416
5.  Long Noncoding RNAs-Related Diseases, Cancers, and Drugs 
The Scientific World Journal  2013;2013:943539.
Long noncoding RNA (lncRNA) function is described in terms of related gene expressions, diseases, and cancers as well as their polymorphisms. Potential modulators of lncRNA function, including clinical drugs, natural products, and derivatives, are discussed, and bioinformatic resources are summarized. The improving knowledge of the lncRNA regulatory network has implications not only in gene expression, diseases, and cancers, but also in the development of lncRNA-based pharmacology.
doi:10.1155/2013/943539
PMCID: PMC3690748  PMID: 23843741
6.  Marine algal natural products with anti-oxidative, anti-inflammatory, and anti-cancer properties 
For their various bioactivities, biomaterials derived from marine algae are important ingredients in many products, such as cosmetics and drugs for treating cancer and other diseases. This mini-review comprehensively compares the bioactivities and biological functions of biomaterials from red, green, brown, and blue-green algae. The anti-oxidative effects and bioactivities of several different crude extracts of algae have been evaluated both in vitro and in vivo. Natural products derived from marine algae protect cells by modulating the effects of oxidative stress. Because oxidative stress plays important roles in inflammatory reactions and in carcinogenesis, marine algal natural products have potential for use in anti-cancer and anti-inflammatory drugs.
doi:10.1186/1475-2867-13-55
PMCID: PMC3674937  PMID: 23724847
Algae; ROS; Antioxidant; Inflammation; Antinociceptive; Anti-cancer
7.  Alternative Splicing for Diseases, Cancers, Drugs, and Databases 
The Scientific World Journal  2013;2013:703568.
Alternative splicing is a major diversification mechanism in the human transcriptome and proteome. Several diseases, including cancers, have been associated with dysregulation of alternative splicing. Thus, correcting alternative splicing may restore normal cell physiology in patients with these diseases. This paper summarizes several alternative splicing-related diseases, including cancers and their target genes. Since new cancer drugs often target spliceosomes, several clinical drugs and natural products or their synthesized derivatives were analyzed to determine their effects on alternative splicing. Other agents known to have modulating effects on alternative splicing during therapeutic treatment of cancer are also discussed. Several commonly used bioinformatics resources are also summarized.
doi:10.1155/2013/703568
PMCID: PMC3674688  PMID: 23766705
8.  Golden Berry-Derived 4β-hydroxywithanolide E for Selectively Killing Oral Cancer Cells by Generating ROS, DNA Damage, and Apoptotic Pathways 
PLoS ONE  2013;8(5):e64739.
Background
Most chemotherapeutic drugs for killing cancer cells are highly cytotoxic in normal cells, which limits their clinical applications. Therefore, a continuing challenge is identifying a drug that is hypersensitive to cancer cells but has minimal deleterious effects on healthy cells. The aims of this study were to evaluate the potential of 4β-hydroxywithanolide (4βHWE) for selectively killing cancer cells and to elucidate its related mechanisms.
Methodology and Principal Findings
Changes in survival, oxidative stress, DNA damage, and apoptosis signaling were compared between 4βHWE-treated oral cancer (Ca9-22) and normal fibroblast (HGF-1) cells. At 24 h and 48 h, the numbers of Ca9-22 cells were substantially decreased, but the numbers of HGF-1 cells were only slightly decreased. Additionally, the IC50 values for 4βHWE in the Ca9-22 cells were 3.6 and 1.9 µg/ml at 24 and 48 h, respectively. Time-dependent abnormal increases in ROS and dose-responsive mitochondrial depolarization can be exploited by using 4βHWE in chemotherapies for selectively killing cancer cells. Dose-dependent DNA damage measured by comet-nuclear extract assay and flow cytometry-based γ-H2AX/propidium iodide (PI) analysis showed relatively severer damage in the Ca9-22 cells. At both low and high concentrations, 4βHWE preferably perturbed the cell cycle in Ca9-22 cells by increasing the subG1 population and arrest of G1 or G2/M. Selective induction of apoptosis in Ca9-22 cells was further confirmed by Annexin V/PI assay, by preferential expression of phosphorylated ataxia-telangiectasia- and Rad3-related protein (p-ATR), and by cleavage of caspase 9, caspase 3, and poly ADP-ribose polymerase (PARP).
Conclusions/Significance
Together, the findings of this study, particularly the improved understanding of the selective killing mechanisms of 4βHWE, can be used to improve efficiency in killing oral cancer cells during chemoprevention and therapy.
doi:10.1371/journal.pone.0064739
PMCID: PMC3660349  PMID: 23705007
9.  Anti-proliferative effect of methanolic extract of Gracilaria tenuistipitata on oral cancer cells involves apoptosis, DNA damage, and oxidative stress 
Background
Methanolic extracts of Gracilaria tenuistipitata (MEGT) were obtained from the edible red algae. Previously, we found that water extract of G. tenuistipitata was able to modulate oxidative stress-induced DNA damage and its related cellular responses.
Methods
In this study, the methanol extraction product MEGT was used to evaluate the cell growth inhibition in oral cancer cells and its possible mechanism was investigated.
Results
The cell viability of MEGT treated Ca9-22 oral cancer cell line was significantly decreased in a dose–response manner (p < 0.05). The sub-G1 population and annexin V intensity of MEGT-treated Ca9-22 cancer cells were significantly increased in a dose–response manner (p < 0.0005 and p < 0.001, respectively). The γH2AX intensities of MEGT-treated Ca9-22 cancer cells were significantly increased in a dose–response manner (p < 0.05). The reactive oxygen species (ROS) and glutathione (GSH)-positive intensities of MEGT-treated Ca9-22 oral cancer cells were significantly increased and decreased, respectively, in a dose–response manner (p < 0.05). The DiOC2(3) intensity for mitochondrial membrane potential (MMP) of MEGT-treated Ca9-22 cancer cells was significantly decreased in a dose–response manner (p < 0.05).
Conclusions
These results indicated that MEGT had apoptosis-based cytotoxicity against oral cancer cells through the DNA damage, ROS induction, and mitochondrial depolarization. Therefore, MEGT derived from the edible algae may have potential therapeutic effects against oral squamous cell carcinoma (OSCC).
doi:10.1186/1472-6882-12-142
PMCID: PMC3495219  PMID: 22937998
Red algae; Oral cancer; Apoptosis; γ-H2AX; ROS; Mitochondrial membrane potential; Glutathione

Results 1-9 (9)