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1. This study demonstrated aloe-emodin- and emodin-induced apoptosis in lung carcinoma cell lines CH27 (human lung squamous carcinoma cell) and H460 (human lung non-small cell carcinoma cell). Aloe-emodin- and emodin-induced apoptosis was characterized by nuclear morphological changes and DNA fragmentation. 2. During apoptosis, an increase in cytochrome c of cytosolic fraction and activation of caspase-3, identified by the cleavage of its proform, were observed. 3. To elucidate whether the expression of protein kinase C (PKC) isozymes are involved in aloe-emodin- and emodin-induced apoptosis, this study examined the changes of PKC isozymes by Western blotting techniques during aloe-emodin- and emodin-induced apoptosis. 4. The expression of PKC isozymes involved in aloe-emodin- and emodin-induced apoptosis of CH27 and H460 cells. In this study, aloe-emodin and emodin induced the changes of each of PKC isozymes in CH27 and H460 cells. 5. The decrease in the expression of PKC delta and epsilon may play a critical role in aloe-emodin- and emodin-induced apoptosis in CH27 and H460 cells. 6. The present study also demonstrated that PKC stimulation occurs at a site downstream of caspase-3 in the emodin-mediated apoptotic pathway.

Recent genomewide association studies have identified several prostate cancer susceptibility variants. However, the association between these variants and biochemical failure in prostate cancer patients receiving radical prostatectomy has not been determined. We systematically evaluated 20 prostate cancer-associated single-nucleotide polymorphisms in a cohort of 320 localized prostate cancer patients receiving radical prostatectomy. Each single-nucleotide polymorphism found to be associated with the recurrence of prostate-specific antigen was further analyzed by Kaplan-Meier analysis and Cox regression model. Three prostate cancer susceptibility single-nucleotide polymorphisms (rs1447295 at 8q24, rs7920517 and rs10993994 at 10q11) were associated with prostate-specific antigen recurrence (P < 0.02). Of these, rs7920517 and rs10993994, which were in strong linkage disequilibrium (r 2 = 0.91), also showed significant associations with poor prostate-specific antigen-free survival following radical prostatectomy (log-rank test; P < 0.01). The associations remained significant in our multivariate Cox proportional hazards analysis after adjusting for other clinicopathologic risk covariates (P < 0.01). In conclusion, loci associated with risk for prostate cancer, such as rs7920517 and rs10993994, might also be used to predict the recurrence of prostate-specific antigen in prostate cancer patients receiving radical prostatectomy.

1 Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is an active component from the root and rhizome of Rheum palmatum that has been reported to exhibit antitumour e ects, but the mechanism is not known. The study investigated the e ects and mechanisms of emodin-induced cell death in human lung squamous carcinoma cell line CH27. 2 Emodin (50 mM)-induced CH27 cell apoptosis was con®rmed by cell morphological change, sub-G 1 formation in¯ow cytometry analysis, viability assay and degradation of focal adhesion kinase in this study. 3 Emodin-induced apoptosis of CH27 cells does not involve modulation of endogenous Bcl-X L protein expression, but appears to be associated with the increased expression of cellular Bak and Bax proteins. This study also demonstrated the translocation of Bak and Bax from cytosolic to particulate fractions. 4 This study has shown that emodin-treated CH27 cells revealed the increases in the relative abundance of cytochrome c for the indicated time intervals in cytosolic fraction. 5 This study demonstrates that the activation of caspase-3, caspase-9 and caspase-8 is an important determinant of apoptotic death induced by emodin. 6 These results suggested that emodin induces CH27 cell death by Bax death pathway and Fas pathway.

Purpose: Recent evidence indicates that small noncoding RNA molecules, known as microRNAs (miRNAs), are involved in cancer initiation and progression. We hypothesized that genetic variations in miRNAs and miRNA target sites could be associated with the efficacy of androgen-deprivation therapy (ADT) in men with prostate cancer.Experimental Design: We systematically evaluated 61 common single nucleotide polymorphisms (SNPs) inside miRNAs and miRNA target sites in a cohort of 601 men with advanced prostate cancer treated with ADT. The prognostic significance of these SNPs on disease progression, prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) after ADT were assessed by Kaplan-Meier analysis and Cox regression model.Results: Four, seven, and four SNPs were significantly associated with disease progression, PCSM, and ACM, respectively, after ADT in univariate analysis. KIF3C rs6728684, CDON rs3737336, and IFI30 rs1045747 genotypes remained as significant predictors for disease progression; KIF3C rs6728684, PALLD rs1071738, GABRA1 rs998754, and SYT9 rs4351800 remained as significant predictors for PCSM; and SYT9 rs4351800 remained as a significant predictor for ACM in multivariate models that included clinicopathologic predictors. Moreover, strong combined genotype effects on disease progression and PCSM were also observed. Patients with a greater number of unfavorable genotypes had a shorter time to progression and worse prostate cancer-specific survival during ADT (P for trend < 0.001).Conclusion: SNPs inside miRNAs and miRNA target sites have a potential value to improve outcome prediction in prostate cancer patients receiving ADT.

Ganoderma lucidum is one of most widely used herbal medicine and functional food in Asia, and ganoderic acids (GAs) are its active ingredients. Regulation of GA biosynthesis and enhancing GA production are critical to using G. lucidum as a medicine. However, regulation of GA biosynthesis by various signaling remains poorly understood. This study investigated the role of apoptosis signaling on GA biosynthesis and presented a novel approach, namely apoptosis induction, to increasing GA production. Aspirin was able to induce cell apoptosis in G. lucidum, which was identified by terminal deoxynucleotidyl transferase mediated dUPT nick end labeling assay positive staining and a condensed nuclear morphology. The maximum induction of lanosta-7,9(11), 24-trien-3α-01-26-oic acid (ganoderic acid 24, GA24) production and total GA production by aspirin were 2.7-fold and 2.8-fold, respectively, after 1 day. Significantly lower levels of GA 24 and total GAs were obtained after regular fungal culture for 1.5 months. ROS accumulation and phosphorylation of Hog-1 kinase, a putative homolog of MAPK p38 in mammals, occurred after aspirin treatment indicating that both factors may be involved in GA biosynthetic regulation. However, aspirin also reduced expression of the squalene synthase and lanosterol synthase coding genes, suggesting that these genes are not critical for GA induction. To the best of our knowledge, this is the first report showing that GA biosynthesis is linked to fungal apoptosis and provides a new approach to enhancing secondary metabolite production in fungi.

Aloe-emodin (1,8-dihydroxy-3-(hydroxymethyl)-anthraquinone) is an active component from the root and rhizome of Rheum palmatum that has been reported to exhibit antitumor effects through an unknown mechanism. Our study investigated the mechanisms of aloe-emodin-induced cell death in the human lung nonsmall cell carcinoma cell line H460. Aloe-emodin (40 M)-induced apoptosis of H460 cells involves modulation of cAMP-dependent protein kinase, protein kinase C, Bcl-2, caspase-3 and p38 protein expression. Rheum palmatum L. has been used in Chinese medicine for a long time. Previous treatments of diseases with herbs were empirical more than theoretical. Therefore, clarifying the mechanisms of action of the components of herbs may be important for developing their applications. Aloe-emodin, an active component of the root and rhizome of Rheum palmatum L., 1 has been demonstrated to possess anti-tumor activity. [2][3][4] The mechanisms of the aloeemodin-produced anticancer effects, however, remain unknown. The present study served to investigate the mechanisms of aloeemodin-induced apoptosis on human nonsmall cell lung carcinoma cell H460.Apoptosis is a major form of cell death, which involves many factors such as expression and translocation of Bcl-2 family proteins, activation of caspases, expression of protein kinase C (PKC) family, cAMP-dependent protein kinase (PKA) and mitogen-activated protein kinase (MAP kinase) members signal transduction pathways. The Bcl-2 family proteins, such as Bcl-2, Bcl-X L , Bak and Bax, are the best-characterized regulators of apoptosis. 4,5 Caspases, a family of cysteine proteases, play a critical role during apoptosis. There are at least two major mechanisms (one involving caspase-8 and the other involving caspase-9) 6,7 that directly or indirectly activate "effector" caspases such as caspase-3. 8,9 Many investigators have reported that activation of cAMP signaling is involved in apoptosis. 10,11 The role of cAMP in various cell responses is mediated by the cAMP-dependent protein kinase. The dissociation, however, of catalytic subunit from inactive PKA is the marker of the activity of PKA. The present study determined the change of PKAc (PKA catalytic subunit) in aloe-emodininduced apoptosis. PKC represents 11 isozymes that have been implicated in the regulation of apoptosis. 12,13 The contribution of individual PKC isozymes to this process, however, is not well understood. Many reports suggested that the degradation of ␦PKC was directly concerned in apoptosis in all of the PKC isozymes. 13,14 The relationship between activation of caspase and ␦PKC was investigated in many reports. These reports suggest that ␦PKC should lie upstream or downstream of caspase-3. 13,14 We examined the changes of ␦PKC and caspase-3 and the specificity of the PKC-caspase-3 relationship on aloe-emodin-induced apoptosis.The mitogen-activated protein kinase (MAP kinase) members can be grouped into 3 major classes: the extracellular signalregulated protein kinases (ERKs), the c-jun N-terminal kinases (JNKs) ...

Recent evidence indicates that microRNAs might participate in prostate cancer initiation, progression and treatment response. Germline variations in microRNAs might alter target gene expression and modify the efficacy of prostate cancer therapy. To determine whether genetic variants in microRNAs and microRNA target sites are associated with the risk of biochemical recurrence (BCR) after radical prostatectomy (RP). We retrospectively studied two independent cohorts composed of 320 Asian and 526 Caucasian men with pathologically organ-confined prostate cancer who had a median follow-up of 54.7 and 88.8 months after RP, respectively. Patients were systematically genotyped for 64 single-nucleotide polymorphisms (SNPs) in microRNAs and microRNA target sites, and their prognostic significance on BCR was assessed by Kaplan-Meier analysis and Cox regression model. After adjusting for known clinicopathologic risk factors, two SNPs (MIR605 rs2043556 and CDON rs3737336) remained associated with BCR. The numbers of risk alleles showed a cumulative effect on BCR [perallele hazard ratio (HR) 1.60, 95% confidence interval (CI) 1.16-2.21, p for trend 5 0.005] in Asian cohort, and the risk was replicated in Caucasian cohort (HR 1.55, 95% CI 1.15-2.08, p for trend 5 0.004) and in combined analysis (HR 1.57, 95% CI 1.26-1.96, p for trend <0.001). Results warrant replication in larger cohorts. This is the first study demonstrating that SNPs in microRNAs and micro-RNA target sites can be predictive biomarkers for BCR after RP.