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Guttiferone E (GE) is a benzophenone found in Brazilian red propolis. In the present study, the effect of GE on human (A-375) and murine (B16-F10) melanoma cells was investigated. GE significantly reduced the cellular viability of melanoma cells in a time-dependent manner. In addition, GE demonstrated antiproliferative effect, with IC50 values equivalent to 9.0 and 6.6 µM for A-375 and B16-F10 cells, respectively. The treatment of A-375 cells with GE significantly increased cell populations in G0/G1 phase and decreased those in G2/M phase. Conversely, on B16-F10 cells, GE led to a significant decrease in the populations of cells in G0/G1 phase and concomitantly an increase in the population of cells in phase S. A significantly higher percentage of apoptotic cells was observed in A-375 (43.5%) and B16-F10 (49.9%) cultures after treatment with GE. Treatments with GE caused morphological changes and significant decrease to the melanoma cellsʼ density. GE (10 µM) inhibited the migration of melanoma cells, with a higher rate of inhibition in B16-F10 cells (73.4%) observed. In addition, GE significantly reduced the adhesion of A375 cells, but showed no effect on B16-F10. Treatment with GE did not induce changes in P53 levels in A375 cultures. Molecular docking calculations showed that GE is stable in the active sites of the tubulin dimer with a similar energy to taxol chemotherapy. Taken together, the data suggest that GE has promising antineoplastic potential against melanoma. [ABSTRACT FROM AUTHOR]

Despite the efficacy of chemotherapy, the adverse effects of chemotherapeutic drugs are considered a limitation of leukemia treatment. Therefore, a chemotherapy drug with minimal side effects is currently needed. One interesting molecule for this purpose is a bioactive peptide isolated from plants since it has less toxicity to normal cells. In this study, we extracted protein from the Zingiber officinale rhizome and performed purification to acquire the peptide fraction with the highest cytotoxicity using ultrafiltration, reverse-phase chromatography, and off-gel fractionation to get the peptide fraction that contained the highest cytotoxicity. Finally, a novel antileukemic peptide, P2 (sequence: RALGWSCL), was identified from the highest cytotoxicity fraction. The P2 peptide reduced the cell viability of NB4, MOLT4, and Raji cell lines without an effect on the normal peripheral blood mononuclear cells. The combination of P2 and daunorubicin significantly decreased leukemic cell viability when compared to treatment with either P2 or daunorubicin alone. In addition, leukemic cells treated with P2 demonstrated increased apoptosis and upregulation of caspase 3, 8, and 9 gene expression. Moreover, we also examined the effects of P2 on p53, which is the key regulator of apoptosis. Our results showed that treatment of leukemic cells with P2 led to the upregulation of p53 and Bcl-2-associated X protein, and the downregulation of B-cell lymphoma 2, indicating that p53 is involved in apoptosis induction by P2. The results of this study are anticipated to be useful for the development of P2 as an alternative drug for the treatment of leukemia. [ABSTRACT FROM AUTHOR]

Antcin-A (ATA) is a steroid-like phytochemical isolated from the fruiting bodies of a precious edible mushroom Antrodia cinnamomea. We previously showed that ATA has strong anti-inflammatory and anti-tumor effects; however, other possible bioactivities of this unique compound remain unexplored. In the present study, we aimed to investigate the modulation of epithelial-to-mesenchymal transition (EMT), anti-migration, and anti-invasive potential of ATA against human breast cancer cells in vitro. Human breast cancer cell lines, MCF-7 and MDA-MB-231, were incubated with ATA for 24 h. Wound healing, trans-well invasion, western blot, q-PCR, F-actin staining, and immunofluorescence assays were performed. We found that treatment with ATA significantly blocked EMT processes, as evidenced by upregulation of epithelial markers (E-cadherin and occludin) and downregulation of mesenchymal markers (N-cadherin and vimentin) via suppression of their transcriptional repressor ZEB1. Next, we found that ATA could induce miR-200c, which is a known player of ZEB1 repression. Further investigations revealed that ATA-mediated induction of miR-200c is associated with transcriptional activation of p53, as confirmed by the fact that ATA failed to induce miR-200c or suppress ZEB1 activity in p53 inhibited cells. Further in vitro wound healing and trans-well invasion assays support that ATA could inhibit migratory and invasive potentials of breast cancer cells, and the effect was likely associated with induced phenotypic modulation. Taken together, the present study suggests that antcin-A could be a lead phyto-agent for the development of anti-metastatic drug for breast cancer treatment. [ABSTRACT FROM AUTHOR]

Highlights • We model the biphasic modulation of p53 activity by hepatitis C virus core protein. • Direct interaction between HCV core and p53 cannot explain the data by itself. • A hitherto unknown factor may exist, which inhibits p53 and is HCV coreactivated. • Implications on the ability of an infected cell to repair DNA damage are explored. • The hypothesized factor is a potential biomarker for HCV-to-HCC progression. Abstract Hepatitis C virus (HCV) infection has reached epidemic proportions worldwide. Individuals with chronic HCV infection and without access to treatment are at high risk for developing hepatocellular carcinoma (HCC), a liver cancer that is rapidly fatal after diagnosis. A number of factors have been identified that contribute to HCV-driven carcinogenesis such as scarring of the liver, and chronic inflammation. Recent evidence indicates a direct role for HCV-encoded proteins themselves in oncogenesis of infected hepatocytes. The viral protein HCV core has been shown to interact directly with the host tumor suppressor protein p53, and to modulate p53-activity in a biphasic manner. Here, biochemically-motivated mathematical models of HCV-p53 interactions are developed to elucidate the mechanisms underlying this phenomenon. We show that by itself, direct interaction between HCV core and p53 is insufficient to recapitulate the experimental data. We postulate the existence of an additional factor, activated by HCV core that inhibits p53 function. We present experimental evidence in support of this hypothesis. The model including this additional factor reproduces the experimental results, validating our assumptions. Finally, we investigate what effect HCV core-p53 interactions could have on the capacity of an infected hepatocyte to repair damage to its DNA. Integrating our model with an existing model of the oscillatory response of p53 to DNA damage predicts a biphasic relationship between HCV core and the transformative potential of infected hepatocytes. In addition to providing mechanistic insights, these results suggest a potential biomarker that could help in identifying those HCV patients most at risk of progression to HCC. [ABSTRACT FROM AUTHOR]

Co-delivery of chemical drugs and therapeutic genes for synergistic therapy provides a promising strategy to treat devastating diseases. However, the real-time coordination patterns between chemical drugs and therapeutic genes remain poorly understood. Herein, the complexes of doxorubicin/graphene oxide-polyethyleneimine/p53 plasmid (Dox/GO-PEI/p53) were fabricated and employed to investigate the synergistic manner between Dox and p53 in the inhibition of HeLa cell growth. GO was conjugated with PEI to form the GO-PEI backbone as the delivery vector. The GO backbone provided surfaces with a high specific area to load Dox via the π-π stacking interaction, and was able to release Dox significantly faster at pH 5.0 than at pH 7.0, while the positively charged PEI section of GO-PEI could condense plasmids into GO-PEI/DNA nanoparticles via the electrostatic interaction. The nanoparticles efficiently mediated the transfection of DNA in HeLa cells, with lower cytotoxicity compared to PEI/DNA nanoparticles. Furthermore, the complexes of Dox/GO-PEI/p53 released Dox and expressed p53 gene in a sequential manner, and showed successive inhibition of the in vitro growth of HeLa cells. This type of drug/GO-PEI/DNA complex can be employed as a platform to investigate the coordination pattern between chemical drugs and therapeutic genes for tumor therapy. [ABSTRACT FROM AUTHOR]

Blackmores Symposium - Integrating Complementary Medicine into Pharmacy Practice. Interview with Sir David Lane, Chief Scientist in A*STAR Singapore. What are the Major Cancer Types in China? Why is it so? Interview with Dr Zhao Ping, Chairman, Cancer Foundation of China. A Talk with Farahida Mohd Farid, General Manager of National Cancer Council Malaysia. [ABSTRACT FROM AUTHOR]

Plants living under extreme conditions have developed a strategy to protect their DNA and other important cell structures from environmental stress factors. In particular, watermelon (Citrullus lanatus) has adapted well to extreme conditions. Its survival strategy can be used in the field of skin care, as shown by several tests, including a direct DNA protection assay, the comet assay, and 8-oxo-guanine and p53 detection. [ABSTRACT FROM AUTHOR]

The electrostatic potential plays a key role in many biological processes like determining the affinity of a ligand to a given protein target, and they are responsible for the catalytic activity of many enzymes. Understanding the effect that amino acid mutations will have on the electrostatic potential of a protein, will allow a thorough understanding of which residues are the most important in a protein. MutantElec, is a friendly web application for in silico generation of site-directed mutagenesis of proteins and the comparison of electrostatic potential between the wild type protein and the mutant(s), based on the three-dimensional structure of the protein. The effect of the mutation is evaluated using different approach to the traditional surface map. MutantElec provides a graphical display of the results that allows the visualization of changes occurring at close distance from the mutation and thus uncovers the local and global impact of a specific change. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Abstract: We study the effect of noise on p53 regulatory network, the core of a cell''s modulator for switching between survival and apoptosis. We find that the fluctuations, originating from stochastic expression of p53-responsive genes, introduce marked advantages for the system to sense external stimuli and sustain the function of switches. The coherence between a stimulus and the system''s response undergoes a maximum with the raise of noise level, indicating the occurrence of stochastic resonance. The biological significance of our results is discussed. [Copyright &y& Elsevier]

The article cites a research study conducted by researcher D.S. Dickens and his colleagues and published in the "Journal of Pediatric Hematology Oncology," where successful treatment of an unresectable choroid plexus carcinoma in a patient with Li-Fraumeni syndrome has been reported. Choroid plexus carcinoma is an uncommon central nervous system tumor requiring complete surgical excision for favorable outcome. Following a partial resection of the tumor the patient received chemotherapy consisting of cyclophosphamide, etoposide, and carboplatin.

The article cites a study which reports about successful treatment of an unresectable choroid plexus carcinoma in a patient with Li-Fraumeni syndrome. Choroid plexus carcinoma (CPC) is an uncommon central nervous system tumor requiring complete surgical excision for favorable outcome. Researchers D.S. Dickens and colleagues report the successful treatment of a 2-year-old patient with widely disseminated CPC and Li-Fraumeni syndrome. Following a partial resection of the tumor the patient received chemotherapy consisting of cyclophosphamide, etoposide, and carboplatin. Dickens and colleagues published their study in the "Journal of Pediatric Hematology Oncology."

Study reports the induction of cellular senescence of human colon cancer cells HCT116 upon curcumin treatment. Senescence of HCT116 cells was accompanied by autophagy, confirmed by observations of autophagosomes in the curcumin-treated cells as well as LC3-I I expression, punctue staining of LC3 and increased content of acidic vacuoles. Inhibition of autophagy, due to the diminished expression of ATG5 by RNAi decreased the number of senescent cells induced by curcumin, but not to increased cell death. Results suggest antitumor activity of curcumin and a functional link between senescence and autophagy in curcumin-treated cells. [ABSTRACT FROM AUTHOR]