Research Topics
Species | GARY FIRESTONESummaryAffiliation: University of California Country: USA Publications
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Publications
Arecoline induced disruption of expression and localization of the tight junctional protein ZO-1 is dependent on the HER 2 expression in human endometrial Ishikawa cellsSarbani Giri
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA
BMC Cell Biol 11:53. 2010..Furthermore, in any system, virtually nothing is known about the cellular effects of arecoline treatment on membrane associated signaling components of human cancer cells...
Minireview: modulation of hormone receptor signaling by dietary anticancer indolesGary L Firestone
Department of Molecular and Cell Biology, The University of California at Berkeley, 94720 3200, USA
Mol Endocrinol 23:1940-7. 2009..The focus of this review is to discuss the evidence that directly links the anticancer actions of these two indole compounds to the control of steroid receptor and growth factor receptor signaling...
Anticancer activities of artemisinin and its bioactive derivativesGary L Firestone
Department of Molecular and Cell Biology and The Cancer Research Laboratory, The University of California at Berkeley, CA 94720 3200, USA
Expert Rev Mol Med 11:e32. 2009..This review provides a comprehensive discussion of these cellular responses, and considers the ramifications for the potential development of artemisinin-based compounds in anticancer therapeutic and preventative strategies...
1-Benzyl-indole-3-carbinol is a novel indole-3-carbinol derivative with significantly enhanced potency of anti-proliferative and anti-estrogenic properties in human breast cancer cellsHanh H Nguyen
Department of Molecular and Cell Biology and The Cancer Research Laboratory, Univ of California at Berkeley, Berkeley, CA 94720 3200, United States
Chem Biol Interact 186:255-66. 2010....
Indole-3-carbinol inhibition of androgen receptor expression and downregulation of androgen responsiveness in human prostate cancer cellsJocelyn C Hsu
Department of Molecular and Cell Biology, The University of California at Berkeley, CA 94720, USA
Carcinogenesis 26:1896-904. 2005..Taken together, our results demonstrate that I3C represses AR expression and responsiveness in LNCaP cells as a part of its antiproliferative mechanism...
Indole-3-carbinol mediated cell cycle arrest of LNCaP human prostate cancer cells requires the induced production of activated p53 tumor suppressor proteinJocelyn C Hsu
Department of Molecular and Cell Biology and The Cancer Research Laboratory, The University of California at Berkeley, Berkeley, CA 94720, USA
Biochem Pharmacol 72:1714-23. 2006..Taken together, our results establish that the I3C induced G1 arrest of human prostate cancer cells requires the induced production of the activated phosphorylated forms of p53, which stimulate transcription of the CDK2 inhibitor p21...
Indole-3-carbinol activates the ATM signaling pathway independent of DNA damage to stabilize p53 and induce G1 arrest of human mammary epithelial cellsChristine T Brew
Department of Molecular and Cell Biology and The Cancer Research Laboratory, University of California at Berkeley, Berkeley, CA 94720-3200, USA
Int J Cancer 118:857-68. 2006....
Indole-3-carbinol induces a G1 cell cycle arrest and inhibits prostate-specific antigen production in human LNCaP prostate carcinoma cellsJoann Zhang
Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720-3200, USA
Cancer 98:2511-20. 2003..These findings implicate this dietary indole as a potential chemotherapeutic agent for controlling the growth of human prostate carcinoma cells...
Expression of the serum- and glucocorticoid-inducible protein kinase, Sgk, is a cell survival response to multiple types of environmental stress stimuli in mammary epithelial cellsMeredith L L Leong
Department of Molecular and Cell Biology and The Cancer Research Laboratory, The University of California at Berkeley, Berkeley, California 94720 3200, USA
J Biol Chem 278:5871-82. 2003..Taken together, our study establishes that induction of enzymatically active Sgk functions as a key cell survival component in response to different environmental stress stimuli...
The stimulus-dependent co-localization of serum- and glucocorticoid-regulated protein kinase (Sgk) and Erk/MAPK in mammary tumor cells involves the mutual interaction with the importin-alpha nuclear import proteinPatricia Buse
Department of Molecular and Cell Biology and The Cancer Research Laboratory, University of California at Berkeley, Berkeley, CA 94720 3200, USA
Exp Cell Res 313:3261-75. 2007..We therefore propose that the signal-dependent co-localization of Sgk and Erk/MAPK mediated by importin-alpha represents a new pathway of signal integration between steroid and serum/growth factor-regulated pathways...
Plant-derived 3,3'-Diindolylmethane is a strong androgen antagonist in human prostate cancer cellsHien T Le
Department of Nutritional Sciences and Toxicology, The University of California, Berkeley, California 94720 3104, USA
J Biol Chem 278:21136-45. 2003..To our knowledge, DIM is the first example of a pure androgen receptor antagonist from plants...
Stimulus-dependent regulation of serum and glucocorticoid inducible protein kinase (SGK) transcription, subcellular localization and enzymatic activityGary L Firestone
Department of Molecular and Cell Biology, and The Cancer Research Laboratory, University of California at Berkeley, Berkeley, CA 94720 3200, USA
Cell Physiol Biochem 13:1-12. 2003..Thus, multiple signal transduction pathways converge on SGK to control its availability, function and access to its substrates and non-substrate targets...
Indole-3-carbinol and 3-3'-diindolylmethane antiproliferative signaling pathways control cell-cycle gene transcription in human breast cancer cells by regulating promoter-Sp1 transcription factor interactionsGary L Firestone
Department of Molecular and Cell Biology and Cancer Research Laboratory, University of California at Berkeley, Berkeley, CA 94720 3200, USA
J Nutr 133:2448S-2455S. 2003....
Direct inhibition of elastase activity by indole-3-carbinol triggers a CD40-TRAF regulatory cascade that disrupts NF-kappaB transcriptional activity in human breast cancer cellsIda Aronchik
Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720 3200, USA
Cancer Res 70:4961-71. 2010..Furthermore, we have established a new I3C-mediated antiproliferative cascade that has significant therapeutic potential for treatment of human cancers associated with high levels of elastase and its CD40 membrane substrate...
Indole-3-carbinol stimulates transcription of the interferon gamma receptor 1 gene and augments interferon responsiveness in human breast cancer cellsUrmi Chatterji
Department of Molecular and Cell Biology and The Cancer Research Laboratory, University of California at Berkeley, Berkeley, CA 94720-3200, USA
Carcinogenesis 25:1119-28. 2004..Our results suggest that one mechanism by which I3C mediates these anticancer effects is by stimulating expression of the IFNgammaR1 and augmenting the IFNgamma response in MCF-7 human breast cancer cells...
Importin-alpha mediates the regulated nuclear targeting of serum- and glucocorticoid-inducible protein kinase (Sgk) by recognition of a nuclear localization signal in the kinase central domainAnita C Maiyar
Department of Molecular and Cell Biology and The Cancer Research Laboratory, University of California at Berkeley, 94720 3200, USA
Mol Biol Cell 14:1221-39. 2003..Our results define a new role importin-alpha in the stimulus-dependent control of signal transduction by nuclear localized protein kinases...
Glucocorticoid-induced degradation of glycogen synthase kinase-3 protein is triggered by serum- and glucocorticoid-induced protein kinase and Akt signaling and controls beta-catenin dynamics and tight junction formation in mammary epithelial tumor cellsKim L Failor
Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720 3200, USA
Mol Endocrinol 21:2403-15. 2007....
Indole-3-carbinol triggers aryl hydrocarbon receptor-dependent estrogen receptor (ER)alpha protein degradation in breast cancer cells disrupting an ERalpha-GATA3 transcriptional cross-regulatory loopCrystal N Marconett
Department of Molecular and Cell Biology, University of California Berkeley, CA 94720, USA
Mol Biol Cell 21:1166-77. 2010....
Artemisinin selectively decreases functional levels of estrogen receptor-alpha and ablates estrogen-induced proliferation in human breast cancer cellsShyam N Sundar
Department of Molecular and Cell Biology and The Cancer Research Laboratory, University of California at Berkeley, Berkeley, CA 94720, USA
Carcinogenesis 29:2252-8. 2008....
Indole-3-carbinol inhibits MDA-MB-231 breast cancer cell motility and induces stress fibers and focal adhesion formation by activation of Rho kinase activityChristine T Brew
Department of Molecular and Cell Biology, The University of California at Berkeley, Berkeley, CA 94720 3200, USA
Int J Cancer 124:2294-302. 2009..Taken together, our data demonstrate that I3C induces stress fibers and peripheral focal adhesions in a Rho kinase-dependent manner that leads to an inhibition of motility in human breast cancer cells...
N-Alkoxy derivatization of indole-3-carbinol increases the efficacy of the G1 cell cycle arrest and of I3C-specific regulation of cell cycle gene transcription and activity in human breast cancer cellsSarah M Jump
Department of Molecular and Cell Biology and The Cancer Research Laboratory, University of California at Berkeley, Berkeley, CA 94720 3200, USA
Biochem Pharmacol 75:713-24. 2008....
Selective glucocorticoid control of Rho kinase isoforms regulate cell-cell interactionsNicola M Rubenstein
Department of Molecular and Cell Biology, The Cancer Research Laboratory, University of California at Berkeley, 591 LSA, Berkeley, CA 94720 3200, USA
Biochem Biophys Res Commun 354:603-7. 2007..Taken together, our results demonstrate that the expression and activity of ROCK1 and ROCK2 can be uncoupled in a signal-dependent manner, and further implicate a new function for ROCK2 in the steroid control of tight junction dynamics...
Indole-3-carbinol (I3C) inhibits cyclin-dependent kinase-2 function in human breast cancer cells by regulating the size distribution, associated cyclin E forms, and subcellular localization of the CDK2 protein complexHanh H Garcia
Department of Molecular and Cell Biology and The Cancer Research Laboratory, The University of California at Berkeley, Berkeley, California 94720, USA
J Biol Chem 280:8756-64. 2005....
Pilot study: effect of 3,3'-diindolylmethane supplements on urinary hormone metabolites in postmenopausal women with a history of early-stage breast cancerKathie M Dalessandri
Department of Molecular and Cell Biology, University of California, Berkeley, 94720-3200, USA
Nutr Cancer 50:161-7. 2004..020), DIM (P =0. 045), and cortisol (P = 0.039), and a nonsignificant increase of 47% in the 2-OHE1/16alpha-OHE1 ratio from 1.46 to 2.14 (P=0.059). In this pilot study, DIM increased the 2-hydroxylation of estrogen urinary metabolites...
Glucocorticoids control beta-catenin protein expression and localization through distinct pathways that can be uncoupled by disruption of signaling events required for tight junction formation in rat mammary epithelial tumor cellsYi Guan
Department of Molecular and Cell Biology, 591 LSA, University of California at Berkeley, Berkeley, California 94720 3200, USA
Mol Endocrinol 18:214-27. 2004....
Glucocorticoid down-regulation of RhoA is required for the steroid-induced organization of the junctional complex and tight junction formation in rat mammary epithelial tumor cellsNicola M Rubenstein
Department of Molecular and Cell Biology and The Cancer Research Laboratory, University of California at Berkeley, 94720-3200, USA
J Biol Chem 278:10353-60. 2003....
Transforming growth factor-alpha abrogates the glucocorticoid stimulation of tight junction formation and reverses the steroid-induced down-regulation of fascin in rat mammary epithelial tumor cells by a Ras-dependent pathwayYi Guan
Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California, 94720 3200, USA
Exp Cell Res 273:1-11. 2002..We propose that reversing the down-regulation of fascin is critical for the ability of TGF-alpha to disrupt the glucocorticoid-induced remodeling of the apical junction that leads to tight junction formation...
Rnd3/RhoE induces tight junction formation in mammary epithelial tumor cellsNicola M Rubenstein
Department of Molecular and Cell Biology and The Cancer Research Laboratory, University of California, Berkeley, CA 94720 3200, USA
Exp Cell Res 305:74-82. 2005..Our results demonstrate a new role for the Rho family member Rnd3/RhoE in regulating the assembly of the apical junction complex and tight junction sealing...
Indole-3-carbinol selectively uncouples expression and activity of estrogen receptor subtypes in human breast cancer cellsShyam N Sundar
Department of Molecular and Cell Biology, 591 LSA, University of California at Berkeley, Berkeley, California 94720-3200 USA
Mol Endocrinol 20:3070-82. 2006....
Fate of indole-3-carbinol in cultured human breast tumor cellsRichard E Staub
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, California 94720, USA
Chem Res Toxicol 15:101-9. 2002..The accumulation of DIM in the nucleus suggests that this product may have a role in the cellular biological activities of I3C.3..
Bcl-2 family-mediated apoptotic effects of 3,3'-diindolylmethane (DIM) in human breast cancer cellsChibo Hong
Department of Nutritional Sciences and Toxicology, University of California, Berkeley 94720-3200, USA
Biochem Pharmacol 63:1085-97. 2002..These results demonstrate that DIM can induce apoptosis in breast cancer cells independent of estrogen receptor status by a process that is mediated by the modulated expression of the Bax/Bcl-2 family of apoptotic regulatory factors...
3,3'-Diindolylmethane (DIM) induces a G(1) cell cycle arrest in human breast cancer cells that is accompanied by Sp1-mediated activation of p21(WAF1/CIP1) expressionChibo Hong
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720, USA
Carcinogenesis 23:1297-305. 2002..Thus, our observations have uncovered an antiproliferative pathway for DIM that implicates Sp1/Sp3-induced expression of p21 as a target for cell cycle control in human breast cancer cells...
Activation and potentiation of interferon-gamma signaling by 3,3'-diindolylmethane in MCF-7 breast cancer cellsJacques E Riby
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, 94720-3104, USA
Mol Pharmacol 69:430-9. 2006..These results reveal novel immune activating and potentiating activities of DIM in human tumor cells that may contribute to the established effectiveness of this dietary indole against various tumors types...
Potent ligand-independent estrogen receptor activation by 3,3'-diindolylmethane is mediated by cross talk between the protein kinase A and mitogen-activated protein kinase signaling pathwaysHoyee Leong
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, California 94720, USA
Mol Endocrinol 18:291-302. 2004..These results demonstrate that DIM is a mechanistically novel activator of the ER that requires PKA-dependent phosphorylation of CREB...
Estrogen receptor beta inhibits human breast cancer cell proliferation and tumor formation by causing a G2 cell cycle arrestSreenivasan Paruthiyil
Department of Obstetrics, University of California, San Francisco, CA 94143 0556, USA
Cancer Res 64:423-8. 2004..Natural or synthetic ERbeta-selective estrogens may lack breast cancer promoting properties exhibited by estrogens in hormone replacement regimens and may be useful for chemoprevention of breast cancer...
3,3'-diindolylmethane reduces levels of HIF-1alpha and HIF-1 activity in hypoxic cultured human cancer cellsJacques E Riby
Department of Nutritional Sciences and Toxicology, 217 Morgan Hall, University of California, Berkeley, CA 94720, USA
Biochem Pharmacol 75:1858-67. 2008..These studies are the first to show that DIM can decrease the accumulation and activity of the key angiogenesis regulatory factor, HIF-1alpha, in hypoxic tumor cells...
3,3'-Diindolylmethane is a novel mitochondrial H(+)-ATP synthase inhibitor that can induce p21(Cip1/Waf1) expression by induction of oxidative stress in human breast cancer cellsYixuan Gong
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, California 94720, USA
Cancer Res 66:4880-7. 2006..Thus, we have established the critical role of enhanced mitochondrial ROS release in 3,3'-diindolylmethane-induced p21 up-regulation in human breast cancer cells...
3,3'-Diindolylmethane inhibits angiogenesis and the growth of transplantable human breast carcinoma in athymic miceXiaofei Chang
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720, USA
Carcinogenesis 26:771-8. 2005..This is the first study to show that DIM can strongly inhibit the development of human breast tumor in a xenograft model and to provide evidence for the antiangiogenic properties of this dietary indole...
DIM stimulates IFNgamma gene expression in human breast cancer cells via the specific activation of JNK and p38 pathwaysLing Xue
Department of Nutritional Sciences and Toxicology, University of California, 119 Morgan Hall, Berkeley, CA 94720-3104, USA
Oncogene 24:2343-53. 2005..These results establish that DIM-induced IFNgamma expression in human breast tumor cells is mediated by activation of both JNK and p38 pathways, which is ultimately dependent on intracellular calcium signaling...
Inhibition of growth factor-induced Ras signaling in vascular endothelial cells and angiogenesis by 3,3'-diindolylmethaneXiaofei Chang
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720, USA
Carcinogenesis 27:541-50. 2006..These data provide evidence that DIM inhibits Ras signaling induced by VEGF and other growth factors, which interferes with its downstream biological effects necessary for angiogenesis...
DEVD-NucView488: a novel class of enzyme substrates for real-time detection of caspase-3 activity in live cellsHui Cen
Biotium, Inc, 3423 Investment Blvd, Ste 8, Hayward, CA 94545, USA
FASEB J 22:2243-52. 2008..The strategy utilized in the design of this fluorogenic substrate can be applied in future endeavors to develop substrates for detecting real-time intracellular enzyme activity...
3,3'-diindolylmethane is a novel topoisomerase IIalpha catalytic inhibitor that induces S-phase retardation and mitotic delay in human hepatoma HepG2 cellsYixuan Gong
Department of Nutritional Sciences and Toxicology, 119 Morgan Hall, University of California, Berkeley, CA 94720-3104, USA
Mol Pharmacol 69:1320-7. 2006..Our results identified a new mode of action for this intriguing dietary component that might be exploited for therapeutic development...
3,3'-Diindolylmethane stimulates murine immune function in vitro and in vivoLing Xue
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720 3104, USA
J Nutr Biochem 19:336-44. 2008..Thus, DIM is a potent stimulator of immune function. This property might contribute to the cancer inhibitory effects of this indole...
Research Grants
- Transcriptional & cell cycle control by dietary indolesGARY FIRESTONE; Fiscal Year: 2007..This information will be particularly valuable to develop new classes of I3C-based therapeutics for reproductive cancers. ..
- REGULATORY BIOLOGY OF CANCER AND GROWTH CONTROLGARY FIRESTONE; Fiscal Year: 2007....
- STEROID CONTROL OF EPITHELIAL CELL-CELL INTERACTIONSGARY FIRESTONE; Fiscal Year: 2007..abstract_text> ..
- STEROID CONTROL OF EPITHELIAL CELL-CELL INTERACTIONSGARY FIRESTONE; Fiscal Year: 2003....
- POSTTRANSLATIONAL RESPONSES OF STEROID HORMONESGARY FIRESTONE; Fiscal Year: 1999....
- POSTTRANSLATION RESPONSES OF STEROID HORMONESGARY FIRESTONE; Fiscal Year: 1992....
- STEROID CONTROL OF EPITHELIAL CELL-CELL INTERACTIONSGary L Firestone; Fiscal Year: 2010..A final goal is to functionally characterize the roles of GSK3 and CAS and their degradative systems in the steroid dependent control of beta-catenin dynamics, apical junction organization and tight junction formation. ..
