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https://www.readbyqxmd.com/read/28527150/development-of-in-silico-protocols-to-predict-structural-insights-into-the-metabolic-activation-pathways-of-xenobiotics
#1
M Kalim A Khan, Salman Akhtar, Jamal M Arif
To establish in silico model to predict the structural insight into the metabolic bioactivation pathway of xenobiotics, we considered two specific and one non-specific mammary procarcinogen [e.g., dibenzo[a,l]pyrene (DBP), 7,12-dimethylbenz[a]anthracene (DMBA), and benzo[a]pyrene (BP)]. The CYP1A1, 1B1, 2C9, 1A2 and 2B6 reported in wet-lab studies to actively metabolize DBP also showed strong binding energies (kcal/mol) of -11.50, -10.67, -10.37, -9.76 and -9.72, respectively, with inhibition constants ranging between 0...
May 19, 2017: Interdisciplinary Sciences, Computational Life Sciences
https://www.readbyqxmd.com/read/28515436/nimbolide-upregulates-reck-by-targeting-mir-21-and-hif-1%C3%AE-in-cell-lines-and-in-a-hamster-oral-carcinogenesis-model
#2
Jaganathan Kowshik, Rajakishore Mishra, Josephraj Sophia, Satabdi Rautray, Kumaraswamy Anbarasu, G Deepak Reddy, Madhulika Dixit, Sundarasamy Mahalingam, Siddavaram Nagini
Reversion-inducing cysteine-rich protein with Kazal motifs (RECK), a potent inhibitor of matrix metalloproteinases (MMPs) is a common negative target of oncogenic signals and a potential therapeutic target for novel drug development. Here, we show that sequential RECKlessness stimulates angiogenesis and Notch signalling in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis model, a paradigm for oral oncogenesis and chemointervention. We also report the chemotherapeutic effect of nimbolide, a limonoid from the neem tree (Azadirachta indica) based on the upregulation of RECK as well as modulation of the expression of key molecules involved in invasion and angiogenesis...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28514181/folic-acid-modulates-dmba-tpa-induced-changes-in-skin-of-mice-a-study-relevant-to-carcinogenesis
#3
Ashwani Koul, Navneet Kaur, Neha Arora Chugh
The present study was aimed at investigating the modulatory effects of folic acid (FA) on early stages of chemically induced skin cancer. For this, a two-stage model of skin tumorigenesis was employed. 7,12-Dimethylbenz(a)anthracene (DMBA, 500 nmol/100 ul of acetone) was applied topically for two weeks (twice weekly), followed by phorbol-12-myristate-13-acetate (TPA, 1.7 nmol/100 ul) twice weekly for six weeks on the depilated skin of mice, and FA was administered orally at a dose of 40 microgram/animal for 10 weeks daily...
May 17, 2017: Journal of Dietary Supplements
https://www.readbyqxmd.com/read/28511374/assessment-of-lipid-peroxidation-and-antioxidant-status-in-vanillic-acid-treated-7-12-dimethylbenz-a-anthracene-induced-hamster-buccal-pouch-carcinogenesis
#4
Vinoth Anbalagan, Kowsalya Raju, Manoharan Shanmugam
INTRODUCTION: Vanillic acid, a naturally occurring bioactive substance, possesses diverse pharmacological potential including free radical scavenging and anticancer properties. Excessive generation of Reactive Oxygen Species (ROS) and insufficient antioxidant potential has been involved in numerous pathological disorders, including cancer. AIM: To explore the anti-lipid peroxidative and antioxidant efficacy of vanillic acid in Dimethylbenz[a]Anthracene (DMBA) induced oral carcinogenesis...
March 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28507113/efficacy-of-a-binuclear-cyclopalladated-compound-therapy-for-cutaneous-leishmaniasis-in-the-murine-model-of-infection-with-leishmania-amazonensis-and-its-inhibitory-effect-on-topoisomerase-1b
#5
Angela Maria Arenas Velásquez, Willian Campos Ribeiro, Vutey Venn, Silvia Castelli, Mariana Santoro, Renata Pires de Assis, Rodrigo Alves de Souza, Aline Rimoldi Ribeiro, Thaís Gaban Passalaqua, João Aristeu da Rosa, Amanda Martins Baviera, Antonio Eduardo Mauro, Alessandro Desideri, Elmo Eduardo Almeida-Amaral, Marcia A S Graminha
Leishmaniasis is a disease found throughout the (sub)tropical parts of the world caused by protozoan parasites of the Leishmania genus. Despite the numerous problems associated with existing treatments, pharmaceutical companies continue to neglect the development of better ones. The high toxicity of current drugs combined with emerging resistance makes the discovery of new therapeutic alternatives urgent. Here we report the evaluation of a binuclear cyclopalladated complex containing Pd(II) and N,N' -dimethylbenzylamine (Hdmba) against Leishmania amazonensis...
May 15, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28506198/naturally-occurring-benzoic-acid-derivatives-retard-cancer-cell-growth-by-inhibiting-histone-deacetylases-hdac
#6
Preethi G Anantharaju, Bandi Deepa Reddy, Mahesh A Padukudru, Ch M Kumari Chitturi, Manjunath G Vimalambike, SubbaRao V Madhunapantula
Histone deacetylases (HDACs), which modulate the expression of genes, are potential therapeutic targets in several cancers. Targeted inhibition of HDAC prevents the expression of oncogenes thereby help in the treatment of cancers. Hence, several pharmaceutical companies developed inhibitors of HDAC and tested them in preclinical models and in clinical trials. SAHA (suberanilohydroxamic acid) is one such HDAC inhibitor developed for treating breast and colorectal carcinomas. However, due to poor efficacy in clinical trials the utility of SAHA for treating cancers was discouraged...
May 16, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28501931/effect-of-allyl-isothiocyanate-on-nf-%C3%AE%C2%BAb-signaling-in-7-12-dimethylbenz-a-anthracene-and-n-methyl-n-nitrosourea-induced-mammary-carcinogenesis
#7
Thangarasu Rajakumar, Pachaiappan Pugalendhi, Rajendran Jayaganesh, Dhanabalan Ananthakrishnan, Krishnaswamy Gunasekaran
BACKGROUND: Inflammation plays a pivotal role in the process of carcinogenesis and phytochemicals have anti-inflammatory properties gaining more importance in cancer chemoprevention. The present study aimed to investigate the anti-inflammatory effect of allyl isothiocyanate (AITC) on 7,12-dimethylbenz(a)anthracene (DMBA)- and N-methyl-N-nitrosourea (MNU)-induced mammary carcinogenesis in female Sprague-Dawley rats. METHODS: RT-PCR and western blot analysis showed that inflammatory markers such as NF-κB p65, TNF-α, and IL-6 were overexpressed in mammary tumor tissues...
May 13, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/28490774/dmba-acts-on-cumulus-cells-to-desynchronize-nuclear-and-cytoplasmic-maturation-of-pig-oocytes
#8
Zhi-Qiang Song, Xuan Li, Yan-Kui Wang, Zhi-Qiang Du, Cai-Xia Yang
As an environmental pollutant and carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA) can destroy ovarian follicles at all developmental stages in rodents. However, the underlying molecular mechanism remains obscure. In the present study, we aim to address how DMBA affects the in vitro maturation and development of porcine oocytes. We discovered that for 20 μM DMBA-treated cumulus-oocyte complexes (COCs), the rate of oocyte germinal vesicle breakdown (GVBD) was significantly altered, and the extrusion rate of first polar body was increased...
May 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28489060/the-effect-of-vpa-on-increasing-radiosensitivity-in-osteosarcoma-cells-and-primary-culture-cells-from-chemical-carcinogen-induced-breast-cancer-in-rats
#9
Guochao Liu, Hui Wang, Fengmei Zhang, Youjia Tian, Zhujun Tian, Zuchao Cai, David Lim, Zhihui Feng
This study explored whether valproic acid (VPA, a histone deacetylase inhibitor) could radiosensitize osteosarcoma and primary-culture tumor cells, and determined the mechanism of VPA-induced radiosensitization. The working system included osteosarcoma cells (U2OS) and primary-culture cells from chemical carcinogen (DMBA)-induced breast cancer in rats; and clonogenic survival, immunofluorescence, fluorescent in situ hybridization (FISH) for chromosome aberrations, and comet assays were used in this study. It was found that VPA at the safe or critical safe concentration of 0...
May 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28479355/disturbance-of-mammary-udp-glucuronosyltransferase-represses-estrogen-metabolism-and-exacerbates-experimental-breast-cancer
#10
Xueyan Zhou, Ziqiang Zheng, Chang Xu, Juan Wang, Mengjun Min, Yun Zhao, Xi Wang, Yinhan Gong, Jiale Yin, Meng Guo, Dong Guo, Junnian Zheng, Bei Zhang, Xiaoxing Yin
The progression of breast cancer is closely related to the levels of estrogens within the body. UDP-Glucuronosyltransferase (UGT) is an important class of phase II metabolizing enzymes, playing a pivotal role in detoxifying steroid hormone. In the present study we aim to uncover the potential dysregulation pattern of UGT and its role in estrogen metabolism and in the pathogenesis of breast cancer. Female Sprague-Dawley rats were treated with 100 mg/kg dimethylbenz(a)anthracene (DMBA) to induce breast cancer...
May 4, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28457144/molecular-effects-of-hesperetin-a-citrus-flavanone-on7-12-dimethylbenz-a-anthracene-induced-buccal-pouch-squamous-cell-carcinoma-in-golden-syrian-hamsters
#11
Sukumar Babukumar, Veerasamy Vinothkumar, Periyannan Velu, Duraisamy Ramachandhiran, Madhavan Ramados Nirmal
In recent years, researchers have been focused on citrus flavanone, a naturally occurring bioactive substance of hesperetin. To investigate the molecular mechanism based chemopreventive efficacy of hesperetin on 7,12-dimethylbenz(a)anthracene (DMBA) induced hamster buccal pouch (HBP) squamous cell carcinoma (SCC). The oral tumour was provoked by painted with 0.5% DMBA on left buccal pouch thrice a week for 10 consecutive weeks developed well-differentiated SCC and tumour formation was 100% in DMBA alone. We evaluated the chemopreventive potential of hesperetin by assessing the lipid peroxidation (LPO) by-products, status of enzymatic, non-enzymatic antioxidants, detoxifying agents etc...
May 1, 2017: Archives of Physiology and Biochemistry
https://www.readbyqxmd.com/read/28454269/bone-marrow-derived-dendritic-cells-under-influence-of-experimental-breast-cancer-and-physical-activity
#12
Douglas R Abdalla, Bruno B M Gomes, Eddie F C Murta, Márcia A Michelin
Immune cells are required in the immune response against tumours, although sometimes without success. The present study aimed to investigate dendritic cell (DC) maturation in animals with induced immunosuppression that were subjected to physical activity (PA). Immunosuppression was induced using 7,12-dimethyl-benzanthracene (DMBA). A total of 56 Balb/c mice were divided into four groups, including the control group, non-DMBA administered/PA group (GII), DMBA administered/non-PA group (GIII) and the DMBA administered/PA group (GIV)...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28452959/anti-inflammatory-mechanism-involved-in-pomegranate-mediated-prevention-of-breast-cancer-the-role-of-nf-%C3%AE%C2%BAb-and-nrf2-signaling-pathways
#13
Animesh Mandal, Deepak Bhatia, Anupam Bishayee
Pomegranate (Punica granatum L.), a nutrient-rich unique fruit, has been used for centuries for the prevention and treatment of various inflammation-driven diseases. Based on our previous study, a characterized pomegranate emulsion (PE) exhibited a striking inhibition of dimethylbenz(a)anthracene (DMBA)-initiated rat mammary tumorigenesis via antiproliferative and apoptosis-inducing mechanisms. The objective of the present work is to investigate the anti-inflammatory mechanism of action of PE during DMBA rat mammary carcinogenesis by evaluating the expression of cyclooxygenase-2 (COX-2), heat shock protein 90 (HSP90), nuclear factor-κB (NF-κB) and nuclear factor erythroid 2p45 (NF-E2)-related factor 2 (Nrf2)...
April 28, 2017: Nutrients
https://www.readbyqxmd.com/read/28431282/the-role-of-pharmacologic-modulation-of-autophagy-on-anal-cancer-development-in-an-hpv-mouse-model-of-carcinogenesis
#14
Brooks L Rademacher, Kristina A Matkowskyj, Louise M Meske, Alexis Romero, Hana Sleiman, Evie H Carchman
Autophagy is an intracellular, catabolic process that maintains cellular health. We examined the response of pharmacologic modulation of autophagy in an HPV mouse model of anal carcinogenesis. K14E6/E7 mice were treated with the topical carcinogen DMBA weekly and assessed for tumors over 20 weeks. Concurrently, they were given either chloroquine or BEZ235, to inhibit or induce autophagy, respectively. Time to tumor onset was examined. Immunofluorescence (IF) was performed for LC3β and p62 to examine autophagy...
April 18, 2017: Virology
https://www.readbyqxmd.com/read/28427009/early-in-life-dietary-zinc-deficiency-and-supplementation-and-mammary-tumor-development-in-adulthood-female-rats
#15
Flávia R M da Silva, Tony F Grassi, Joyce R Zapaterini, Lucas T Bidinotto, Luis F Barbisan
Zinc deficiency during pregnancy and postnatal life can adversely increase risk of developing human diseases at adulthood. The present study was designed to evaluate whether dietary zinc deficiency or supplementation during the pregnancy, lactation and juvenile stages interferes in the development of mammary tumors induced by 7,12-dimethylbenzanthracene (DMBA) in female Sprague-Dawley (SD) rats. Pregnant female SD rats were allocated into three groups: zinc-adequate diet (ZnA - 35-mg/kg chow), zinc-deficient diet (ZnD - 3-mg/kg chow) or zinc-supplemented diet (ZnS - 180-mg/kg chow) during gestational day 10 (GD 10) until the litters' weaning...
June 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28420987/curcumin-ameliorates-cisplatin-induced-nephrotoxicity-and-potentiates-its-anticancer-activity-in-sd-rats-potential-role-of-curcumin-in-breast-cancer-chemotherapy
#16
Parveen Kumar, Chandana C Barua, Kunjbihari Sulakhiya, Rajeev Kumar Sharma
Breast malignant neoplastic disease is one of the most complex diseases, as it is a multifactorial disease in which virtually all the targets are instantly or indirectly inter-reliant on each other. Cisplatin (CIS), an inorganic antineoplastic agent is widely utilized in the treatment of various solid tumors including breast cancer. Despite everything, its clinical use is limited, due to ototoxicity, peripheral neuropathy, and nephrotoxicity. The present work was directed to assess the combined result of curcumin (CUR) and CIS in 7, 12-dimethyl benz[a]anthracene (DMBA) induced breast cancer in rats and the prevention of nephrotoxicity induced by the latter...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28416734/the-angiotensin-receptor-blocker-losartan-inhibits-mammary-tumor-development-and-progression-to-invasive-carcinoma
#17
Rhiannon Coulson, Seng H Liew, Angela A Connelly, Nicholas S Yee, Siddhartha Deb, Beena Kumar, Ana C Vargas, Sandra A O'Toole, Adam C Parslow, Ashleigh Poh, Tracy Putoczki, Riley J Morrow, Mariah Alorro, Kyren A Lazarus, Evie F W Yeap, Kelly L Walton, Craig A Harrison, Natalie J Hannan, Amee J George, Colin D Clyne, Matthias Ernst, Andrew M Allen, Ashwini L Chand
Drugs that target the Renin-Angiotensin System (RAS) have recently come into focus for their potential utility as cancer treatments. The use of Angiotensin Receptor Blockers (ARBs) and Angiotensin-Converting Enzyme (ACE) Inhibitors (ACEIs) to manage hypertension in cancer patients is correlated with improved survival outcomes for renal, prostate, breast and small cell lung cancer. Previous studies demonstrate that the Angiotensin Receptor Type I (AT1R) is linked to breast cancer pathogenesis, with unbiased analysis of gene-expression studies identifying significant up-regulation of AGTR1, the gene encoding AT1R in ER+ve/HER2-ve tumors correlating with poor prognosis...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415789/hmga2-translocation-induced-in-skin-tumorigenesis
#18
Yong Li, Xiang-Ying Pi, Kelsey Boland, Sonali Lad, Kelly Johnson, Catherine Verfaillie, Rebecca J Morris
Hmga2 protein, a transcription factor involved in chromatin architecture, is expressed chiefly during development, where it has many key biological functions. When expressed in adult tissues from in various organs, Hmga2 is always related to cancer development. The role of Hmga2 in skin tumorigenesis is, however, not yet understood. We demonstrated that Hmga2 can be found in non-transformed epidermis, specifically located to the membrane of keratinocytes (KCs) in epidermis. Ex vivo culture of KCs and development of skin carcinomas in DMBA and TPA mouse models was associated with translocation of the Hmga2 protein from the membrane into the nucleus, where Hmga2 induced its own expression by binding to the Hmga2 promoter...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28402673/functionalized-lipid-polymer-hybrid-nanoparticles-mediated-codelivery-of-methotrexate-and-aceclofenac-a-synergistic-effect-in-breast-cancer-with-improved-pharmacokinetics-attributes
#19
Neeraj K Garg, Rajeev K Tyagi, Gajanand Sharma, Ashay Jain, Bhupinder Singh, Sanyog Jain, O P Katare
The present study was aimed to coencapsulate methotrexate (MTX) and aceclofenac (ACL) in fucose anchored lipid-polymer hybrid nanoparticles (Fu-LPHNPs) to achieve target specific and controlled delivery for developing therapeutic interventions against breast cancer. The effective combination therapy requires coadministration of drugs to achieve synergistic effect on tumor with minimum adverse effects. Present study investigates the potential of codelivery of MTX and ACL through LPHNPs in MCF-7 and triple negative breast cancer cells (MDA-MB-231)...
May 3, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28398226/melatonin-reduces-angiogenesis-in-serous-papillary-ovarian-carcinoma-of-ethanol-preferring-rats
#20
Yohan Ricci Zonta, Marcelo Martinez, Isabel Cristina C Camargo, Raquel F Domeniconi, Luiz Antonio Lupi Júnior, Patricia Fernanda F Pinheiro, Russel J Reiter, Francisco Eduardo Martinez, Luiz Gustavo A Chuffa
Angiogenesis is a hallmark of ovarian cancer (OC); the ingrowth of blood vessels promotes rapid cell growth and the associated metastasis. Melatonin is a well-characterized indoleamine that possesses important anti-angiogenic properties in a set of aggressive solid tumors. Herein, we evaluated the role of melatonin therapy on the angiogenic signaling pathway in OC of an ethanol-preferring rat model that mimics the same pathophysiological conditions occurring in women. OC was chemically induced with a single injection of 7,12-dimethylbenz(a)anthracene (DMBA) under the ovarian bursa...
April 11, 2017: International Journal of Molecular Sciences
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