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Tocotrienol-treated MCF-7 human breast cancer cells show down-regulation of API5 and up-regulation of MIG6 genes

Ramdas P, Rajihuzzaman M, Veerasenan SD, Selvaduray KR, Nesaretnam K, Radhakrishnan AK

Cancer Genomics Proteomics, 2011 Jan-Feb;8(1):19-31.
PMID: 21289334

Tocotrienols belong to the vitamin E family and have multiple anticancer effects, such as antiproliferative, antioxidant, pro-apoptosis and antimetastatic. This study aimed to identify the genes that are regulated in human breast cancer cells following exposure to various isomers of vitamin E as these may be potential targets for the treatment of breast cancer.

Matched MeSH terms: Gene Expression Regulation, Neoplastic/drug effects*
Andrographolide and 14-deoxy-11, 12-didehydroandrographolide inhibit cytochrome P450s in HepG2 hepatoma cells

Ooi JP, Kuroyanagi M, Sulaiman SF, Muhammad TS, Tan ML

Life Sci, 2011 Feb 28;88(9-10):447-54.
PMID: 21219911 DOI: 10.1016/j.lfs.2010.12.019

Cytochrome P450 (CYP) enzymes have been implicated in a large number of preventable drug-herb interactions. Andrographis paniculata Nees, a tropical herb widely used for various health conditions contains two major diterpenoids, andrographolide and 14-Deoxy-11, 12-Didehydroandrographolide. These compounds were evaluated systematically for their effects on CYP1A2, CYP2D6 and CYP3A4 expressions in HepG2 cells.

Matched MeSH terms: Gene Expression Regulation, Enzymologic/drug effects
Development of a quantitative real-time RT-PCR for kinetic analysis of immediate-early transcripts of rat cytomegalovirus

Loh HS, Mohd-Azmi ML

Acta Virol., 2009;53(4):261-9.
PMID: 19941390

One-step real-time RT-PCR assay was developed for quantification of the immediate-early (IE), namely IE1 and IE2 transcripts of Rat cytomegalovirus (RCMV), strain ALL-03 in rat embryonic fibroblast cells (REF). This in-house SYBR Green I based RT-PCR was shown to have higher amplification efficiency and detection limit as compared to a commercially available real-time RT-PCR kit in quantifying these two transcripts. The quantification histogram revealed the divergence of transcription activities of the two IE genes. The IE1 transcript had a concentration peak at 7 hrs post infection (p.i.), whereas IE2 transcript at 20 hrs p.i. Regulation of IE expression is critical for determination, whether the infection is going to be abortive, lytic or latent. Therefore, this in-house developed quantitative RT-PCR assay offers an alternative for diagnosis and monitoring of the acute cytomegalovirus (CMV) infection directed at IE transcript detection.

Matched MeSH terms: Gene Expression Regulation, Viral*
Expression and alteration of p16 in diffuse large B cell lymphoma

Lee ES, Kim LH, Abdullah WA, Peh SC

Pathobiology, 2010;77(2):96-105.
PMID: 20332669 DOI: 10.1159/000278291

This study aimed to examine (1) the expression of P16 protein relative to sites of presentation, immunophenotypic subgroups and proliferative indices of tumour cells, and (2) the relationship between p16 gene alterations and P16 protein overexpression in 70 cases of diffuse large B cell lymphoma (DLBCL).

Matched MeSH terms: Gene Expression Regulation, Neoplastic*
Isolation and characterization of oil palm constitutive promoter derived from ubiquitin extension protein (uep1) gene

Masura SS, Parveez GK, Ismail I

N Biotechnol, 2010 Sep 30;27(4):289-99.
PMID: 20123048 DOI: 10.1016/j.nbt.2010.01.337

The ubiquitin extension protein (uep1) gene was identified as a constitutively expressed gene in oil palm. We have isolated and characterized the 5' region of the oil palm uep1 gene, which contains an 828 bp sequence upstream of the uep1 translational start site. Construction of a pUEP1 transformation vector, which contains gusA reporter gene under the control of uep1 promoter, was carried out for functional analysis of the promoter through transient expression studies. It was found that the 5' region of uep1 functions as a constitutive promoter in oil palm and could drive GUS expression in all tissues tested, including embryogenic calli, embryoid, immature embryo, young leaflet from mature palm, green leaf, mesocarp and meristematic tissues (shoot tip). This promoter could also be used in dicot systems as it was demonstrated to be capable of driving gusA gene expression in tobacco.

Matched MeSH terms: Gene Expression Regulation, Plant/drug effects
Tocotrienols suppress proinflammatory markers and cyclooxygenase-2 expression in RAW264.7 macrophages

Yam ML, Abdul Hafid SR, Cheng HM, Nesaretnam K

Lipids, 2009 Sep;44(9):787-97.
PMID: 19655189 DOI: 10.1007/s11745-009-3326-2

Tocotrienols are powerful chain breaking antioxidant. Moreover, they are now known to exhibit various non-antioxidant properties such as anti-cancer, neuroprotective and hypocholesterolemic functions. This study was undertaken to investigate the anti-inflammatory effects of tocotrienol-rich fraction (TRF) and individual tocotrienol isoforms namely delta-, gamma-, and alpha-tocotrienol on lipopolysaccharide-stimulated RAW264.7 macrophages. The widely studied vitamin E form, alpha-tocopherol, was used as comparison. Stimulation of RAW264.7 with lipopolysaccharide induced the release of various inflammatory markers. 10 mcirog/ml of TRF and all tocotrienol isoforms significantly inhibited the production of interleukin-6 and nitric oxide. However, only alpha-tocotrienol demonstrated a significant effect in lowering tumor necrosis factor-alpha production. Besides, TRF and all tocotrienol isoforms except gamma-tocotrienol reduced prostaglandin E(2) release. It was accompanied by the down-regulation of cyclooxygenase-2 gene expression by all vitamin E forms except alpha-tocopherol. Collectively, the data suggested that tocotrienols are better anti-inflammatory agents than alpha-tocopherol and the most effective form is delta-tocotrienol.

Matched MeSH terms: Gene Expression Regulation/drug effects
RecA mediated spontaneous deletions of the icaADBC operon of clinical Staphylococcus epidermidis isolates: a new mechanism of phenotypic variations

Nuryastuti T, Henny C, Henk JB, Roel K, Abu TA, Bastiaan PK

Med J Malaysia, 2008 Jul;63 Suppl A:97.
PMID: 19025002

Phenotypic variation in biofilm formation is common in clinical isolates of S. epidermidis. In the current study, nearly 5% of all clinical isolates analysed showed phenotypic variation in biofilm forming ability and electrophoretic mobility (EM). This is the first report of S. epidermidis strains irreversibly switching from biofilm-positive to biofilm-negative phenotype by spontaneous deletion of icaADBC genes which represents a new, possibly common mechanism of phenotypic variation.

Matched MeSH terms: Gene Expression Regulation, Bacterial/genetics*
Fulltext Inhibition of hyphae formation and SIR2 expression in Candida albicans treated with fresh Allium sativum (garlic) extract

Low CF, Chong PP, Yong PV, Lim CS, Ahmad Z, Othman F

J Appl Microbiol, 2008 Dec;105(6):2169-77.
PMID: 19120662 DOI: 10.1111/j.1365-2672.2008.03912.x

The aims of the present study were to determine whether Allium sativum (garlic) extract has any effect on the morphology transformation of Candida albicans, and to investigate whether it could alter the gene expression level of SIR2, a morphogenetic control gene and SAP4, a gene encoding secreted aspartyl proteinase.

Matched MeSH terms: Gene Expression Regulation, Fungal/drug effects
Modulation of cell growth and PPARgamma expression in human colorectal cancer cell lines by ciglitazone

Yaacob NS, Darus HM, Norazmi MN

Exp. Toxicol. Pathol., 2008 Sep;60(6):505-12.
PMID: 18579355 DOI: 10.1016/j.etp.2008.05.006

Studies have shown that ligand activation of peroxisome proliferator-activated receptor gamma (PPARgamma) can induce differentiation and inhibit proliferation of several cancer cells. The present study was performed to investigate the effects of the PPARgamma ligand, ciglitazone, and the involvement of PPARgamma in modulating the growth of human colorectal cancer cells. Lactate dehydrogenase release assay showed that ciglitazone potently inhibited HT-29 (well-differentiated) and COLO-205 (poorly differentiated) colorectal adenocarcinoma cell growth. Measurement of apoptosis by flow cytometry using a fluorescein-conjugated monoclonal antibody against cytokeratin 18 revealed a high induction of apoptosis by ciglitazone in a time-dependent fashion. The expression of PPARgamma1 but not PPARgamma2 mRNA was significantly downregulated as measured by real-time quantitative PCR, and the PPARgamma protein levels were decreased as determined by Western blot analysis. We conclude that ciglitazone treatment suppressed colon cancer cell growth via induction of apoptosis. However, the anticancer effects of ciglitazone may not depend solely on PPARgamma activation.

Matched MeSH terms: Gene Expression Regulation, Neoplastic/drug effects*
Gene expression in human oral squamous cell carcinoma is influenced by risk factor exposure

Cheong SC, Chandramouli GV, Saleh A, Zain RB, Lau SH, Sivakumaren S, et al.

Oral Oncol, 2009 Aug;45(8):712-9.
PMID: 19147396 DOI: 10.1016/j.oraloncology.2008.11.002

Oral squamous cell carcinoma (OSCC) is a world health problem and is associated with exposure to different risk factors. In the west, smoking and alcohol consumption are considered to be the main risk factors whilst in India and southeast Asia, betel quid (BQ) chewing is predominant. In this study, we compared the gene expression patterns of oral cancers associated with BQ chewing to those caused by smoking using Affymetrix microarrays. We found that 281 genes were differentially expressed between OSCC and normal oral mucosa regardless of aetiological factors including MMP1, PLAU, MAGE-D4, GNA12, IFITM3 and NMU. Further, we identified 168 genes that were differentially expressed between the BQ and smoking groups including CXCL-9, TMPRSS2, CA12 and RNF24. The expression of these genes was validated using qPCR using independent tissue samples. The results demonstrate that whilst common genes/pathways contribute to the development of oral cancer, there are also other gene expression changes that are specific to certain risk factors. The findings suggest that different carcinogens activate or inhibit specific pathways during cancer development and progression. These unique gene expression profiles should be taken into consideration when developing biomarkers for future use in prognostic or therapeutic applications.

Matched MeSH terms: Gene Expression Regulation, Neoplastic/physiology*
A genome level survey of Burkholderia pseudomallei immunome expressed during human infection

Su YC, Wan KL, Mohamed R, Nathan S

Microbes Infect., 2008 Oct;10(12-13):1335-45.
PMID: 18761419 DOI: 10.1016/j.micinf.2008.07.034

Burkholderia pseudomallei is the etiological agent of melioidosis, a severe infectious disease of humans and animals. The role of the bacterium's proteins expressed in vivo during human melioidosis continues to remain an enigma. This study's aim was to identify B. pseudomallei target proteins that elicit the humoral immune response in infected humans. A small insert genomic expression library was constructed and immunoscreened to identify peptides that reacted exclusively with melioidosis patients' sera. Sero-positive clones expressing immunogenic peptides were sequenced and annotated, and shown to represent 109 proteins involved in bacterial cell envelope biogenesis, cell motility and secretion, transcription, amino acid, ion and protein metabolism, energy production, DNA repair and unknown hypothetical proteins. Western blot analysis of three randomly selected full-length immunogenic polypeptides with patients' sera verified the findings of the immunome screening. The patients' humoral immune response to the 109 proteins suggests the induction or significant upregulation of these proteins in vivo during human infection and thus may play a role in the pathogenesis of B. pseudomallei. Identification of B. pseudomallei immunogens has shed new light on the elucidation of the bacterium's pathogenesis mechanism and disease severity. These immunogens can be further evaluated as prophylactic and serodiagnostic candidates as well as drug targets.

Matched MeSH terms: Gene Expression Regulation, Bacterial*
Fulltext Hypoglycemic effect of Octomeles sumatrana aqueous extract in streptozotocin-induced diabetic rats and its molecular mechanisms

Azahar MA, Al-Naqeb G, Hasan M, Adam A

Asian Pac J Trop Med, 2012 Nov;5(11):875-81.
PMID: 23146801 DOI: 10.1016/S1995-7645(12)60163-1

OBJECTIVE: To investigate the hypoglycemic effect of the aqueous extract of Octomeles sumatrana (O. sumatrana) (OS) in streptozotocin-induced diabetic rats (STZ) and its molecular mechanisms.
METHODS: Diabetes was induced by intraperitoneal (i.p.) injection of streptozotocin (55 mg/kg) in to male Sprague-Dawley rats. Rats were divided into six different groups; normal control rats were not induced with STZ and served as reference, STZ diabetic control rats were given normal saline. Three groups were treated with OS aqueous extract at 0.2, 0.3 and 0.5 g/kg, orally twice daily continuously for 21 d. The fifth group was treated with glibenclamide (6 mg/kg) in aqueous solution orally continuously for 21 d. After completion of the treatment period, biochemical parameters and expression levels of glucose transporter 2 (Slc2a2), glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PCK1) were determined in liver by quantitative real time PCR.
RESULTS: Administration of OS at different doses to STZ induced diabetic rats, resulted in significant decrease (P<0.05) in blood glucose level in a dose dependent manner by 36%, 48%, and 64% at doses of 0.2, 0.3 and 0.5 g/kg, respectively, in comparison to the STZ control values. Treatment with OS elicited an increase in the expression level of Slc2a2 gene but reduced the expression of G6Pase and PCK1 genes. Morefore, OS treated rats, showed significantly lower levels of serum alanine transaminase (ALT), aspartate aminotransferase (AST) and urea levels compared to STZ untreated rats. The extract at different doses elicited signs of recovery in body weight gain when compared to STZ diabetic controls although food and water consumption were significantly lower in treated groups compared to STZ diabetic control group.
CONCLUSIONS: O. sumatrana aqueous extract is beneficial for improvement of hyperglycemia by increasing gene expression of liver Slc2a2 and reducing expression of G6Pase and PCK1 genes in streptozotocin-induced diabetic rats.

Matched MeSH terms: Gene Expression Regulation/drug effects
Gene expression profiling of p53(+/-) knockout and wild-type mice following diethylstilbestrol administration

Salleh MN, Ismail P, Abdullah AS, Taufiq-Yap YH, Carmichael P

IUBMB Life, 2004 Jul;56(7):409-16.
PMID: 15545218

Studies with clastogenic carcinogen diethylstilbestrol (DES) resulted in a broad of spectrum of toxic and carcinogenic effects in humans and rodents, but the cellular and molecular mechanism(s) by which it induces cancer is not clear. To identify putative genetic targets for p53 in vivo, we applied the cDNA macroarray gene expression profiles associated with apoptosis by comparing p53+/- knockout mice and wild-type mice on the kidney and uterus of female mice. p53+/- knockout mice and wild-type mice were treated with DES (500 micromole kg(-1)) or vehicle i.p once daily for 4 days. Total RNAs were obtained from kidney and uterus of both control and DES-treated. The signal intensities of individual gene spots on the membrane were quantified and normalized to the expression level of the GAPDH gene as an internal control. Our results demonstrated that 16 genes; bad, bax, bcl-2, bcl-w, bcl-x, caspase-3, caspase-7, caspase-8, c-myc, E124, GADD45, mdm2, NKkappab1, p53, p21, Rb and trail were up-regulated and six genes; caspase-1, caspase-2, DR5, E2F1, FasL and iNOS did not changed in response to DES treatment in wild-type mice compared to p53+/- knockout mice. Most genes are involved in cell cycle regulation, signal transduction, apoptosis, or transcription. The greatest changes were seen in bad, bcl-x, mdm2, p53 and p21 gene expression in wild-type mice compared to p53+/- knockout mice. In comparing p53 and p21 gene expression in wild-type mice and p53+/- knockout mice, there was an 4.4-fold vs. 1.8-fold; 8-fold vs. 5.2-fold for kidney and 16-fold vs. 5.5-fold; 2.1-fold vs. 8.3-fold for uterus samples increase in induction (respectively). RT-PCR and densitometric analysis was used to confirm the biggest changes of p21, p53 and bax genes. Using this approach, we have identified apoptosis associated genes regulated in response to DES and have revealed putative differences between the isogenic parent strain and p53+/- knockout mice, which will contribute to a better understanding of toxicity/carcinogenicity mechanisms in this model.

Matched MeSH terms: Gene Expression Regulation/drug effects*
Tocotrienol-rich fraction from palm oil affects gene expression in tumors resulting from MCF-7 cell inoculation in athymic mice

Nesaretnam K, Ambra R, Selvaduray KR, Radhakrishnan A, Reimann K, Razak G, et al.

Lipids, 2004 May;39(5):459-67.
PMID: 15506241

It has recently been shown that tocotrienols are the components of vitamin E responsible for inhibiting the growth of human breast cancer cells in vitro, through an estrogen-independent mechanism. Although tocotrienols act on cell proliferation in a dose-dependent manner and can induce programmed cell death, no specific gene regulation has yet been identified. To investigate the molecular basis of the effect of tocotrienols, we injected MCF-7 breast cancer cells into athymic nude mice. Mice were fed orally with 1 mg/d of tocotrienol-rich fraction (TRF) for 20 wk. At end of the 20 wk, there was a significant delay in the onset, incidence, and size of the tumors in nude mice supplemented with TRF compared with the controls. At autopsy, the tumor tissue was excised and analyzed for gene expression by means of a cDNA array technique. Thirty out of 1176 genes were significantly affected. Ten genes were downregulated and 20 genes up-regulated with respect to untreated animals, and some genes in particular were involved in regulating the immune system and its function. The expression of the interferon-inducible transmembrane protein-1 gene was significantly up-regulated in tumors excised from TRF-treated animals compared with control mice. Within the group of genes related to the immune system, we also found that the CD59 glycoprotein precursor gene was up-regulated. Among the functional class of intracellular transducers/effectors/modulators, the c-myc gene was significantly down-regulated in tumors by TRF treatment. Our observations indicate that TRF supplementation significantly and specifically affects MCF-7 cell response after tumor formation in vivo and therefore the host immune function. The observed effect on gene expression is possibly exerted independently from the antioxidant activity typical of this family of molecules.

Matched MeSH terms: Gene Expression Regulation, Neoplastic/drug effects*
Fulltext Transcriptional profiles of the response of methicillin-resistant Staphylococcus aureus to pentacyclic triterpenoids

Chung PY, Chung LY, Navaratnam P

PLoS One, 2013;8(2):e56687.
PMID: 23437212 DOI: 10.1371/journal.pone.0056687

Staphylococcus aureus is an important human pathogen in both hospital and the community that has demonstrated resistance to all currently available antibiotics over the last two decades. Multidrug-resistant isolates of methicillin-resistant S. aureus (MRSA) exhibiting decreased susceptibilities to glycopeptides has also emerged, representing a crucial challenge for antimicrobial therapy and infection control. The availability of complete whole-genome nucleotide sequence data of various strains of S. aureus presents an opportunity to explore novel compounds and their targets to address the challenges presented by antimicrobial drug resistance in this organism. Study compounds α-amyrin [3β-hydroxy-urs-12-en-3-ol (AM)], betulinic acid [3β-hydroxy-20(29)-lupaene-28-oic acid (BA)] and betulinaldehyde [3β-hydroxy-20(29)-lupen-28-al (BE)] belong to pentacyclic triterpenoids and were reported to exhibit antimicrobial activities against bacteria and fungi, including S. aureus. The MIC values of these compounds against a reference strain of methicillin-resistant S. aureus (MRSA) (ATCC 43300) ranged from 64 µg/ml to 512 µg/ml. However, the response mechanisms of S. aureus to these compounds are still poorly understood. The transcription profile of reference strain of MRSA treated with sub-inhibitory concentrations of the three compounds was determined using Affymetrix GeneChips. The findings showed that these compounds regulate multiple desirable targets in cell division, two-component system, ABC transporters, fatty acid biosynthesis, peptidoglycan biosynthesis, aminoacyl-tRNA synthetase, ribosome and β-lactam resistance pathways which could be further explored in the development of therapeutic agents for the treatment of S. aureus infections.

Matched MeSH terms: Gene Expression Regulation, Bacterial/drug effects
Fulltext Effect of cathepsin D and prostate specific antigen on latent transforming growth factor-beta in breast cancer cell lines

Wong SF, Seow HF, Lai LC

Malays J Pathol, 2003 Dec;25(2):129-34.
PMID: 16196369

Transforming growth factor-beta (TGFbeta) is present, predominantly in latent forms, in normal and malignant breast tissue. The mechanisms by which latent TGFbeta is activated physiologically remain largely an enigma. The objective of this study was to assess whether the proteases, cathepsin D and prostate specific antigen (PSA) could activate latent TGFbeta1 and TGFbeta2 in conditioned media of the hormone-dependent MCF-7 and hormone-independent MDA-MB-231 human breast cancer cell lines, newly purchased from ATCC. Both of the cell lines were seeded in 6-well plates 2 days prior to treatment with varying concentrations of cathepsin D and PSA. Active TGFbeta1 and TGFbeta2 in the media were then measured by ELISA after 4, 8, 24 and 72 hours of treatment. TGFbeta1 and TGFbeta2 mRNA expression of both cell lines were measured by RT-PCR to determine whether any increase in level of active TGFbeta1 and TGFbeta2 was due to increased production. There was a significant increase in only active TGFbeta2 levels in the MDA-MB-231 cell line with both treatments. Cathepsin D and PSA did not have any effect on TGFbeta1 and TGFbeta2 mRNA expression. Cathepsin D and PSA were unable to activate latent TGFbeta1 and TGFbeta2 in these two breast cancer cell lines. A constant level of TGFbeta2 mRNA in the control and treated MDA-MB-231 cells suggests that the increase in level of active TGFbeta2 was not a result of increased production but was likely to be due to activation by a mechanism independent of cathepsin D and PSA.

Matched MeSH terms: Gene Expression Regulation, Neoplastic/drug effects
Strobilanthes crispus Juice Concentrations and Anticancer Effects on DNA Damage, Apoptosis and Gene Expression in Hepatocellular Carcinoma Cells

Hussin F, Eshkoor SA, Rahmat A, Othman F, Akim A, Eshak Z

Asian Pac J Cancer Prev, 2015;16(14):6047-53.
PMID: 26320494

BACKGROUND: Hepatocellular carcinoma is one of the most common cancers worldwide. Its prevalence is increasing in many countries. Plant products can be used to protect against cancer due to natural anticancer and chemopreventive constituents. Strobilanthes crispus is one of plants with potential chemopreventive ability.
OBJECTIVE: This study aimed to evaluate the anticancer effects of Strobilanthes crispus juice on hepatocellular carcinoma cells.
MATERIALS AND METHODS: MTT assays, flow cytometry, comet assays and the reverse transcription- polymerase chain reaction (RT-PCR) were used to determine the effects of juice on DNA damage and cancer cell numbers.
RESULTS: This juice induced apoptosis after exposure of the HepG2 cell line for 72 h. High percentages of apoptotic cell death and DNA damage were seen at the juice concentrations above 0.1%. It was found that the juice was not toxic for normal cells. In addition, juice exposure increased the expression level of c-myc gene and reduced the expression level of c-fos and c-erbB2 genes in HepG2 cells. The cytotoxic effects of juice on abnormal cells were in dose dependent.
CONCLUSIONS: It was concluded that the Strobilanthes crispus juice may have chemopreventive effects on hepatocellular carcinoma cells.

Matched MeSH terms: Gene Expression Regulation, Neoplastic/drug effects*
Human topoisomerase II alpha as a prognostic biomarker in cancer chemotherapy

Ali Y, Abd Hamid S

Tumour Biol., 2016 Jan;37(1):47-55.
PMID: 26482620 DOI: 10.1007/s13277-015-4270-9

Topoisomerases are nuclear enzymes that regulate topology of DNA by facilitating the temporary cleavage and ligation cycle of DNA. Among all forms of topoisomerases, TOP-IIA is extensively associated with cell proliferation and therefore is an important therapeutic target in diseases that involved cellular proliferation such as cancers. Nearly half of present-day antitumor regimens contain at least one prescription that act as a topoisomerase inhibitor. Generally, tumor cells show divergent expression of TOP-IIA compared to normal cells. The remarkable expression of TOP-IIA in various carcinomas provides a significant biomarker toward understanding the nature of malignancy. TOP-IIA expression and amplification studies help in diagnosing cancer and to observe the disease progression, overall survival (OS) of patients, and response to therapy. This review highlights the research output and analysis in exploring the standing of TOP-IIA in various carcinomas. As some reports show contradiction within the same field of interest, the outline of that may help to induce researchers for further investigation and clarification. To the best of our knowledge, this is the first overview briefly summarizing the prognostic feature of TOP-IIA in various types of cancer.

Matched MeSH terms: Gene Expression Regulation, Neoplastic*
Cancer prevention and therapy through the modulation of transcription factors by bioactive natural compounds

Shanmugam MK, Lee JH, Chai EZ, Kanchi MM, Kar S, Arfuso F, et al.

Semin Cancer Biol, 2016 10;40-41:35-47.
PMID: 27038646 DOI: 10.1016/j.semcancer.2016.03.005

The association between chronic inflammation and cancer development has been well documented. One of the major obstacles in cancer treatment is the persistent autocrine and paracrine activation of pro-inflammatory transcription factors such as nuclear factor-κB, signal transducer and activator of transcription 3, activator protein 1, fork head box protein M1, and hypoxia-inducible factor 1α in a wide variety of tumor cell lines and patient specimens. This, in turn, leads to an accelerated production of cellular adhesion molecules, inflammatory cytokines, chemokines, anti-apoptotic molecules, and inducible nitric oxide synthase. Numerous medicinal plant-derived compounds have made a tremendous impact in drug discovery research endeavors, and have been reported to modulate the activation of diverse oncogenic transcription factors in various tumor models. Moreover, novel therapeutic combinations of standard chemotherapeutic drugs with these agents have significantly improved patient survival by making cancer cells more susceptible to chemotherapy and radiotherapy. In this review, we critically analyze the existing literature on the modulation of diverse transcription factors by various natural compounds and provide views on new directions for accelerating the discovery of novel drug candidates derived from Mother Nature.

Matched MeSH terms: Gene Expression Regulation, Neoplastic/drug effects
Fulltext Understanding the dimorphic lifestyles of human gastric pathogen Helicobacter pylori using the SWATH-based proteomics approach

Loke MF, Ng CG, Vilashni Y, Lim J, Ho B

Sci Rep, 2016 05 25;6:26784.
PMID: 27222005 DOI: 10.1038/srep26784

Helicobacter pylori may reside in the human stomach as two morphological forms: the culturable spiral form and the viable but non-culturable (VBNC) coccoid form. This bacterium transforms from spiral to coccoid under in vitro suboptimal conditions. However, both spiral and coccoid have demonstrated its infectivity in laboratory animals, suggesting that coccoid may potentially be involved in the transmission of H. pylori. To determine the relevance of the coccoid form in viability and infectivity, we compared the protein profiles of H. pylori coccoids obtained from prolonged (3-month-old) culture with that of 3-day-old spirals of two H. pylori standard strains using SWATH (Sequential Window Acquisition of all Theoretical mass spectra)-based approach. The protein profiles reveal that the coccoids retained basal level of metabolic proteins and also high level of proteins that participate in DNA replication, cell division and biosynthesis demonstrating that coccoids are viable. Most interestingly, these data also indicate that the H. pylori coccoids possess higher level of proteins that are involved in virulence and carcinogenesis than their spiral counterparts. Taken together, these findings have important implications in the understanding on the pathogenesis of H. pylori-induced gastroduodenal diseases, as well as the probable transmission mode of this bacterium.

Matched MeSH terms: Gene Expression Regulation, Bacterial*

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