Janet V. Cross, Ph.D.
- Molecular Mechanisms of Cancer Chemoprevention
- Anti-Inflammatory Benefits of Dietary Nutrient Compounds
Fresh fruits and vegetables are indisputable components of a healthy diet. However, mechanistic understandings of how food products impact human physiology are few. In addition to essential vitamins and minerals, many vegetables contain chemical compounds that have positive health effects. Among these is the isothiocyanate class of chemicals present in cruciferous vegetables such as broccoli. Isothiocyanates have been well characterized for their activity in preventing tumor development in carcinogen-challenged animals. However, little is know about how these compounds prevent cancer, and whether they may have other beneficial health effects.
The bioactive nutrient isothiocyanates (ITCs) are chemically reactive compounds whose structure suggests that they could covalently modify potential protein targets. Using a novel proteomics screen, we identified a prevalent protein target of ITC modification in the cell. This protein is implicated in the pathogenesis of a number of inflammatory diseases including rheumatoid arthritis, inflammatory bowel disease and asthma where studies have shown that it is a critical participant in the disease process. As a participant in signal transduction, gene expression, apoptosis and proliferation of target cells, this protein is a provocative molecular target for the isothiocyanates that could explain their chemopreventive activity. In addition, the central role of this protein in inflammatory disease processes may indicate a potential anti-inflammatory benefit for these nutrient compounds.
Using two of the most prevalent isothiocyanates in broccoli, sulforaphane and PEITC, we are working to characterize the importance of this protein target in the phenomenon of cancer chemoprevention. In addition, we are using both in vitro studies and animal models to characterize the potential of these compounds to interfere with inflammatory processes in an intact organism. These studies may define a molecular mechanism for action of cancer chemopreventives and allow the development of alternative approaches for cancer prevention. Moreoever, they may provide additional insights into the well-appreciated epidemiological link between inflammation and cancer risk and define a pharmacological target for intervention in these processes.
- Villarreal-Calderon R, LuÃ©vano-GonzÃ¡lez A, AragÃ³n-Flores M, Zhu H, Yuan Y, Xiang Q, Yan B, Stoll KA, Cross JV, Iczkowski KA, Mackinnon AC: Antral atrophy, intestinal metaplasia, and preneoplastic markers in Mexican children with Helicobacter pylori-positive and Helicobacter pylori-negative gastritis. Ann Diagn Pathol 2014, 18:129-135. http://www.ncbi.nlm.nih.gov/pubmed/24656654. DOI: 10.1016/j.anndiagpath.2014.02.003.
- Conine SJ, Cross JV: MIF deficiency does not alter glucose homeostasis or adipose tissue inflammatory cell infiltrates during diet-induced obesity. Obesity (Silver Spring) 2014, 22:418-425.http://www.ncbi.nlm.nih.gov/pubmed/23804488. DOI: 10.1002/oby.20555.
- CalderÃ³n-GarcidueÃ±as L, Cross JV, Franco-Lira M, AragÃ³n-Flores M, Kavanaugh M, Torres-JardÃ³n R, Chao CK, Thompson C, Chang J, Zhu H, D’Angiulli A: Brain immune interactions and air pollution: macrophage inhibitory factor (MIF), prion cellular protein (PrP(C)), Interleukin-6 (IL-6), interleukin 1 receptor antagonist (IL-1Ra), and interleukin-2 (IL-2) in cerebrospinal fluid and MIF in serum differentiate urban children exposed to severe vs. low air pollution. Front Neurosci 2013, 7:183. http://www.ncbi.nlm.nih.gov/pubmed/24133408. DOI: 10.3389/fnins.2013.00183.
- CalderÃ³n-GarcidueÃ±as L, Mora-TiscareÃ±o A, Franco-Lira M, Cross JV, Engle R, AragÃ³n-Flores M, GÃ³mez-Garza G, Jewells V, Medina-Cortina H, Solorio E, Chao CK, Zhu H, Mukherjee PS, Ferreira-Azevedo L, Torres-JardÃ³n R, D’Angiulli A: Flavonol-rich dark cocoa significantly decreases plasma endothelin-1 and improves cognition in urban children. Front Pharmacol 2013, 4:104. http://www.ncbi.nlm.nih.gov/pubmed/23986703. DOI: 10.3389/fphar.2013.00104.
- CalderÃ³n-GarcidueÃ±as L, Serrano-Sierra A, Torres-JardÃ³n R, Zhu H, Yuan Y, Smith D, Delgado-ChÃ¡vez R,Cross JV, Medina-Cortina H, Kavanaugh M, Guilarte TR: The impact of environmental metals in young urbanites’ brains. Exp Toxicol Pathol 2013, 65:503-511. http://www.ncbi.nlm.nih.gov/pubmed/22436577. DOI: 10.1016/j.etp.2012.02.006.
- Simpson KD, Templeton DJ, Cross JV: Macrophage migration inhibitory factor promotes tumor growth and metastasis by inducing myeloid-derived suppressor cells in the tumor microenvironment. J Immunol 2012, 189:5533-5540. http://www.ncbi.nlm.nih.gov/pubmed/23125418. DOI: 10.4049/jimmunol.1201161.
- Simpson KD, Cross JV: MIF: metastasis/MDSC-inducing factor? Oncoimmunology 2013, 2:e23337.http://www.ncbi.nlm.nih.gov/pubmed/23802077. DOI: 10.4161/onci.23337.
- Victor KG, Rady JM, Cross JV, Templeton DJ: Proteomic profile of reversible protein oxidation using PROP, purification of reversibly oxidized proteins. PLoS One 2012, 7:e32527.http://www.ncbi.nlm.nih.gov/pubmed/22389707. DOI: 10.1371/journal.pone.0032527.
- Zhou J, Joplin DG, Cross JV, Templeton DJ: Sulforaphane inhibits prostaglandin E2 synthesis by suppressing microsomal prostaglandin E synthase 1. PLoS One 2012, 7:e49744.http://www.ncbi.nlm.nih.gov/pubmed/23166763. DOI: 10.1371/journal.pone.0049744.
- Lyons CE, Victor KG, Moshnikov SA, Bachmann LM, Baras AS, Dettmann KM, Cross JV, Templeton DJ: PICquant: a quantitative platform to measure differential peptide abundance using dual-isotopic labeling with 12C6- and 13C6-phenyl isocyanate. Anal Chem 2011, 83:856-865.http://www.ncbi.nlm.nih.gov/pubmed/21192683. DOI: 10.1021/ac102461e.
- Gutierrez GJ, Tsuji T, Cross JV, Davis RJ, Templeton DJ, Jiang W, Ronai ZA: JNK-mediated phosphorylation of Cdc25C regulates cell cycle entry and G(2)/M DNA damage checkpoint. J Biol Chem 2010, 285:14217-14228.http://www.ncbi.nlm.nih.gov/pubmed/20220133. DOI: 10.1074/jbc.M110.121848.
- Templeton DJ, Aye MS, Rady J, Xu F, Cross JV: Purification of reversibly oxidized proteins (PROP) reveals a redox switch controlling p38 MAP kinase activity. PLoS One 2010, 5:e15012.http://www.ncbi.nlm.nih.gov/pubmed/21085594. DOI: 10.1371/journal.pone.0015012.
A current list of Dr. Cross’ journal publications can be obtained from PubMed.