THE USE OF MANDAMUS TO COMPEL EDUCATIONAL INSTITUTIONS TO CONFER DEGREES

Hispolon is an active phenolic compound of <i>Phellinus igniarius</i>, a mushroom that was recently shown to have antioxidant and anticancer activities in various solid tumors. Here, the molecular mechanisms by which hispolon exerts anticancer effects in acute myeloid leukemia (AML) cells was investigated. The results showed that hispolon suppressed cell proliferation in the various AML cell lines. Furthermore, hispolon effectively induced apoptosis of HL-60 AML cells through caspases-8, -9, and -3 activations and PARP cleavage. Moreover, treatment of HL-60 cells with hispolon induced sustained activation of JNK1/2, and inhibition of JNK by JNK1/2 inhibitor or JNK1/2-specific siRNA significantly abolished the hispolon-induced activation of the caspase-8/-9/-3. In vivo, hispolon significantly reduced tumor growth in mice with HL-60 tumor xenografts. In hispolon-treated tumors, activation of caspase-3 and a decrease in Ki67-positive cells were observed. Our results indicated that hispolon may have the potential to serve as a therapeutic tool to treat AML

Additional file 1: of Penfluridol triggers cytoprotective autophagy and cellular apoptosis through ROS induction and activation of the PP2A-modulated MAPK pathway in acute myeloid leukemia with different FLT3 statuses

Figure S1. Inhibition of reactive oxygen species (ROS) reverses penfluridol-induced LC3 turnover and p62 degradation in HL-60 acute myeloid leukemia cells. Figure S2. Inhibition of p38 mitogen-activated protein kinase (MAPK) reverses penfluridol-induced extracellular signal-regulated kinase (ERK) dephosphorylation in U937 and HL-60 acute myeloid leukemia cells. (DOCX 166 kb

Distribution frequency of <i>ICAM-1</i> genotypes in 561 healthy controls and 595 oral cancer patients.

<p>The odds ratios (ORs) and with their 95% confidence intervals (CIs) were estimated by logistic regression models. The adjusted odds ratios (AORs) with their 95% confidence intervals (CIs) were estimated by multiple logistic regression models after controlling for age, gender, betel nut chewing, tobacco and alcohol consumption.</p>*<p><i>P</i> value<0.05 as statistically significant.</p

The distributions of demographical characteristics in 561 controls and 595 patients with oral cancer.

<p>Mann-Whitney U test or Fisher's exact test was used between healthy controls and patients with oral cancer.</p>*<p><i>p</i> value<0.05 as statistically significant.</p

TaqMan primer sets for <i>ICAM-1</i> genotyped SNPs.

<p>TaqMan primer sets for <i>ICAM-1</i> genotyped SNPs.</p

Adjusted odds ratio (AOR) and 95% confidence interval (CI) of oral cancer associated with <i>ICAM-1</i> genotypic frequencies and smokers among 549 betel nut consumers.

<p>The odds ratios (ORs) with their 95% confidence intervals were estimated by logistic regression models.</p><p>The adjusted odds ratios (AORs) with their 95% confidence intervals were estimated by multiple logistic regression models after controlling for age, gender and alcohol consumption.</p>a<p>Individual with wild genotype but without smoking.</p>b<p>Individual with either at least one mutated genotype or smoking.</p>c<p>Individual with both at least one mutated genotype and smoking.</p

Distribution frequency of <i>ICAM-1</i> haplotype in controls and oral cancer patients.

#<p>Others: CAGA (54),CACG (53), CTGG (26), TAGA(23), CAGG(19), CTGA(3), TACA (2).</p

Effect of pterostilbene (PTER) on caspase activation and mitochondrial membrane permeability (MMP) in HL-60 cells.

<p>(A) Expression levels of cleaved caspases-3, -8, and -9, and poly (ADP-ribose polymerase (PARP) were assessed by a Western blot analysis after treatment with various concentrations of PTER (0∼150 µM) for 24 h. (B) Quantitative results of cleaved caspase-3, -8, and -9, and PARP protein levels, which were adjusted to the α-tubulin protein level and expressed as multiples of induction beyond each respective control. Values are presented as the mean ± SE of three independent experiments. *^{, #, &, $}<i>p</i><0.05, compared to the vehicle control groups. (C) Activated caspase-9, -8, and -3 protein expression were upregulated in a time-dependent fashion after PTER 100 µM) treatment, peaking at 24 h in HL-60 cells. (D) Effect of a caspase-3 inhibitor on PTER-induced cell death. Cells were treated with 100 µM PTER for 24 h in the presence or absence of 2 µM Z-DEVE-FMK. Cell proliferation was determined by an MTS assay. Data are presented as the mean ± SE of three independent experiments performed in triplicate. *<i>p</i><0.05, control vs. PTER; ^#<i>p</i><0.05, PTER vs. Z-DEVE-FMK plus PTER. (E and F) Loss of the MMP after 24 h of treatment with PTER as determined by FACS and immunofluorescence analyses of JC-1 staining. (E) From the FACS analysis, increased percentages of green fluorescent apoptotic (FL 1) populations of HL-60 at the indicated drug concentrations (cells in the lower right field) are indicated (upper panel). The red-to-green fluorescence ratio indicates functional mitochondria with membrane potential. Data are presented as the mean ± SE of three independent experiments performed in triplicate. *<i>p</i><0.05, control vs. PTER (F) Immunofluorescence analysis showed that green-fluorescent monomeric form increases in HL-60 cells after treatment with 100 µM PTER for 24 h. Original magnification, 200×.</p

Adjusted odds ratio (AOR) and 95% confidence interval (CI) of oral cancer associated with <i>ICAM-1</i> genotypic frequencies and betel nut chewing among 727 smokers.

<p>The odds ratios (ORs) with their 95% confidence intervals were estimated by logistic regression models.</p><p>The adjusted odds ratios (AORs) with their 95% confidence intervals were estimated by multiple logistic regression models after controlling for age, gender and alcohol consumption.</p>a<p>Individual with wild genotype but without betel nut chewing.</p>b<p>Individual with either at least one mutated genotype or betel nut chewing.</p>c<p>Individual with both at least one mutated genotype and betel nut chewing.</p

Hispolon Induces Apoptosis through JNK1/2-Mediated Activation of a Caspase-8, -9, and -3-Dependent Pathway in Acute Myeloid Leukemia (AML) Cells and Inhibits AML Xenograft Tumor Growth in Vivo

Hispolon is an active phenolic compound of <i>Phellinus igniarius</i>, a mushroom that was recently shown to have antioxidant and anticancer activities in various solid tumors. Here, the molecular mechanisms by which hispolon exerts anticancer effects in acute myeloid leukemia (AML) cells was investigated. The results showed that hispolon suppressed cell proliferation in the various AML cell lines. Furthermore, hispolon effectively induced apoptosis of HL-60 AML cells through caspases-8, -9, and -3 activations and PARP cleavage. Moreover, treatment of HL-60 cells with hispolon induced sustained activation of JNK1/2, and inhibition of JNK by JNK1/2 inhibitor or JNK1/2-specific siRNA significantly abolished the hispolon-induced activation of the caspase-8/-9/-3. In vivo, hispolon significantly reduced tumor growth in mice with HL-60 tumor xenografts. In hispolon-treated tumors, activation of caspase-3 and a decrease in Ki67-positive cells were observed. Our results indicated that hispolon may have the potential to serve as a therapeutic tool to treat AML