Chemopreventive effects of pterostilbene through p53 and cell cycle in mouse lung of squamous cell carcinoma model

Cell proliferation and cell death abnormalities are strongly linked to the development of cancer, including lung cancer. The purpose of this study was to investigate the effect of pterostilbene on cell proliferation and cell death via cell cycle arrest during the transition from G1 to S phase and the p53 pathway. A total of 24 female Balb/C mice were randomly categorized into four groups (n = 6): N-nitroso-tris-chloroethyl urea (NTCU) induced SCC of the lungs, vehicle control, low dose of 10 mg/kg PS + NTCU (PS10), and high dose of 50 mg/kg PS + NTCU (PS50). At week 26, all lungs were harvested for immunohistochemistry and Western blotting analysis. Ki-67 expression is significantly lower, while caspase-3 expression is significantly higher in PS10 and PS50 as compared to the NTCU (p < 0.05). There was a significant decrease in cyclin D1 and cyclin E2 protein expression in PS10 and PS50 when compared to the NTCU (p < 0.05). PS50 significantly increased p53, p21, and p27 protein expression when compared to NTCU (p < 0.05). Pterostilbene is a potential chemoprevention agent for lung SCC as it has the ability to upregulate the p53/p21 pathway, causing cell cycle arrest.

Germline genetic variation in prostate susceptibility does not predict outcomes in the chemoprevention trials PCPT and SELECT

Background The development of prostate cancer can be influenced by genetic and environmental factors. Numerous germline SNPs influence prostate cancer susceptibility. The functional pathways in which these SNPs increase prostate cancer susceptibility are unknown. Finasteride is currently not being used routinely as a chemoprevention agent but the long term outcomes of the PCPT trial are awaited. The outcomes of the SELECT trial have not recommended the use of chemoprevention in preventing prostate cancer. This study investigated whether germline risk SNPs could be used to predict outcomes in the PCPT and SELECT trial. Methods Genotyping was performed in European men entered into the PCPT trial (n = 2434) and SELECT (n = 4885). Next generation genotyping was performed using Affymetrix® Eureka™ Genotyping protocols. Logistic regression models were used to test the association of risk scores and the outcomes in the PCPT and SELECT trials. Results Of the 100 SNPs, 98 designed successfully and genotyping was validated for samples genotyped on other platforms. A number of SNPs predicted for aggressive disease in both trials. Men with a higher polygenic score are more likely to develop prostate cancer in both trials, but the score did not predict for other outcomes in the trial. Conclusion Men with a higher polygenic risk score are more likely to develop prostate cancer. There were no interactions of these germline risk SNPs and the chemoprevention agents in the SELECT and PCPT trials.

Caesalpinia sappan L. Ethanolic Extract Decrease Intracellular ROS Level and Senescence of 4T1 Breast Cancer Cells

Highly and uncontrolled cell proliferation on cancer cells may boost ROS level intracellular accumulation up significantly. Sappan heartwood (Caesalpinia sappan L.) have been known to have cytotoxicity effect toward several cancer cells. This research was conducted to develop Caesalpinia sappan L. heartwood ethanolic extract (CSE) as chemopreventive agent which can be used as cancer therapy, looked from antioxidant and anti-senescence activity toward 4T1 breast cancer cell. CSE was obtained through maceration using ethanol 70% as solvent. Cytotoxicity activity of CSE was done by using MTT assay with IC50 as parameter. This IC50 was used as basic to the next assay, ROS assay by using DCFDA staining flowcytometry to look ROS level intracellular of CSE toward 4T1 cell and senescence assay by using senescence associated β-galactosidase (SA β-gal) assay with % cell senescence as their parameter. CSE toxic to 4T1 cell that proved from IC50 value of 25 µg/mL. Single treatment of CSE on concentration 12,5; 25; and 37.5 µg/mL able to suppress ROS level intracellular. If compared with untreated cell, single treatment of CSE on concentration 6 and 12 µg/mL showed % cell senescence not significantly different. Based on this result, CSE is cytotoxic, has antioxidant and antisenescence activity, so it has great potential to developed as chemoprevention agent on cancer therapy.Keywords : Caesalpinia sappan L., 4T1 breast cancer line, Reactive Oxygen Species (ROS), anti-senescence

PPARγ-Mediated p21 Induction in Aerodigestive Preneoplastic Cell Lines

Introduction: Oral leukoplakia is defined as a mucous membrane disorder characterized by white patches that cannot be scraped off. Leukoplakia is the most frequent, potentially premalignant oral mucosa disorder and a good candidate for chemopreventive therapies. Pioglitazone activates peroxisome proliferator–activated receptor gamma (PPARγ), which forms a complex with nuclear cofactors and regulates gene expression of a variety of cell-cycle proteins and is currently being tested preclinically and clinically in aerodigestive cancer prevention. Methods: In the present study, we hypothesized that pioglitazone would decrease proliferation of human leukoplakia cells (MSK Leuk1) and transformed bronchial epithelial cells (BEAS-2B) through regulatory changes of G1 checkpoint protein regulators, p21 and cyclin-D1. MSK Leuk1 and BEAS-2B cells were treated with pioglitazone and assayed for cell proliferation and p21 transcriptional activity. Results: We discovered pioglitazone significantly inhibited cell proliferation in a dose-dependent fashion. We also observed p21 protein induction after treatment with pioglitazone, which was preceded by measurable increases in p21 mRNA induction. Conclusions: We conclude the PPARγ activator, pioglitazone, can activate p21, which is associated with decreased proliferation in 2 aerodigestive preneoplastic cell lines. In addition, the p21 gene may be a potential hypothesis-driven biomarker in translational studies of pioglitazone as a chemoprevention agent for aerodigestive cancer.

ANTIOXIDANT ACTIVITY AND BIOGENIC SYNTHESIS OF SELENIUM NANOPARTICLES USING THE LEAF EXTRACT OF ALOE VERA

Objective: The objective of this present study were to the biogenic synthesis of selenium nanoparticles using Aloe vera extract and check it’s antioxidant potential by ABTS, DPPH and FRAP assays.Methods: In this study we investigated the clove of Aloe vera, which is used for the synthesis of selenium nanoparticles were characterized by using UV-Visible (UV-VIS) spectrophotometer, Transmission electron microscopy (TEM), Fourier transform spectroscopy (FTIR) and Energy dispersive X-Ray spectroscopy (EDAX) and ABTS, DPPH and FRAP assays for checked it’s antioxidant potential.Results: The present study was carried out to synthesis of Selenium nanoparticles using extract of Aloe vera. UV-Vis Spectra at 350 nm with Aloe vera extract and observed as hollow and spherical particles in size ranging 7-48 nm which is found more stable more than two months. EDAX analysis was carried out to check the presoak of Selenium in nanoparticles. Results of EDAX, confirmed its present. TEM and SEAD represented addition evidence of formation of nanoparticles whereas SEAD indicates the particles were crystalline in nature. FT-IR analysis was carried out to identify the possible bio molecules and Aloe vera extract-metal ions interaction responsible for formation and stabilization of selenium nanoparticles. FRAP, ABTS and DPPH assay results sequester that Selenium nanoparticles prepared using Aloe vera extract possess more activity than extract alone.Conclusion: The bio molecules of Aloe veraextract acted as stabilizing as well as capping agent leading to the formation of Selenium nanoparticles. Selenite has been proven to have antioxidant activity and is being used as chemoprevention agent in cancer diagnosis but same time it is toxic also. Elemental Selenium i.e. Selenium nanoparticles are less toxic form of selenium.

Anti-inflammatory and Anti-oxidative Activities of Polyacetylene from Dendropanax dentiger

Dendropanax dentiger has been used as a folk medicine since ancient times. In our current study, we observed that D. dentiger exhibited a significant anti-inflammatory activity, which could efficiently inhibit nitric oxide (NO) production in the lipopolysaccharide (LPS)-induced macrophage inflammation assay. (9 Z,16 S)-16-Hydroxy-9,17-octadecadiene-12,14-diynoic acid (HODA) was isolated from the leaves of D. dentiger following a bioactivity guided fractionation protocol. Our data indicated that HODA significantly inhibited the NO production in LPS-induced RAW 264.7 murine macrophage cells (IC50 = 4.28 μM). Consistent with these observations, the mRNA and protein expression levels of iNOS were also inhibited by HODA in a dose-dependent manner. HODA also reduced the translocation of NF-κB into nuclear fractions. Meanwhile, HODA enhanced Nrf-2 activation and its downstream antioxidant gene HO-1. We concluded that HODA possessed significant anti-inflammatory and anti-oxidative activity; the compound may have a potential for development as a chemoprevention agent.