F P Kuhajda

Johns Hopkins University, Baltimore, Maryland, United States

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Publications (98)545.99 Total impact

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    ABSTRACT: Storage of excess calories as triglycerides is central to obesity and its associated disorders. Glycerol-3-phosphate acyltransferases (GPATs) catalyze the initial step in acylglyceride syntheses, including triglyceride synthesis. We utilized a novel small-molecule GPAT inhibitor, FSG67, to investigate metabolic consequences of systemic pharmacological GPAT inhibition in lean and diet-induced obese (DIO) mice. FSG67 administered intraperitoneally decreased body weight and energy intake, without producing conditioned taste aversion. Daily FSG67 (5 mg/kg, 15.3 μmol/kg) produced gradual 12% weight loss in DIO mice beyond that due to transient 9- to 10-day hypophagia (6% weight loss in pair-fed controls). Continued FSG67 maintained the weight loss despite return to baseline energy intake. Weight was lost specifically from fat mass. Indirect calorimetry showed partial protection by FSG67 against decreased rates of oxygen consumption seen with hypophagia. Despite low respiratory exchange ratio due to a high-fat diet, FSG67-treated mice showed further decreased respiratory exchange ratio, beyond pair-fed controls, indicating enhanced fat oxidation. Chronic FSG67 increased glucose tolerance and insulin sensitivity in DIO mice. Chronic FSG67 decreased gene expression for lipogenic enzymes in white adipose tissue and liver and decreased lipid accumulation in white adipose, brown adipose, and liver tissues without signs of damage. RT-PCR showed decreased gene expression for orexigenic hypothalamic neuropeptides AgRP or NPY after acute and chronic systemic FSG67. FSG67 given intracerebroventricularly (100 and 320 nmol icv) produced 24-h weight loss and feeding suppression, indicating contributions from direct central nervous system sites of action. Together, these data point to GPAT as a new potential therapeutic target for the management of obesity and its comorbidities.
    AJP Regulatory Integrative and Comparative Physiology 04/2011; 301(1):R116-30. · 3.28 Impact Factor
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    Francis P. Kuhajda
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    ABSTRACT: Fatty acid synthase (FAS) inhibition initiates selective apoptosis of cancer cells both in vivo and in vitro, which may involve malonyl-CoA metabolism. These findings led to exploration of malonyl-CoA decarboxylase (MCD) as a potential novel target for cancer treatment. MCD regulates the levels of cellular malonyl-CoA through the decarboxylation of malonyl-CoA to acetyl-CoA. Malonyl-CoA is both a substrate for FAS and an inhibitor of fatty acid oxidation acting as a metabolic switch between anabolic fatty acid synthesis and catabolic fatty acid oxidation. We now report that treatment of human breast cancer (MCF7) cells with MCD small interference RNA (siRNA) reduces MCD expression and activity, reduces ATP levels, and is cytotoxic to MCF7 cells, but not to human fibroblasts. In addition, we synthesized a small molecule inhibitor of MCD, 5-{(Morpholine-4-carbonyl)-[4-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)- phenyl]-amino}-pentanoic acid methyl ester (MPA). Similar to MCD siRNA, MPA inhibits MCD activity in MCF7 cells, increases cellular malonyl-CoA levels and is cytotoxic to a number of human breast cancer cell lines in vitro. Taken together, these data indicate that MCDinduced cytotoxicity is likely mediated through malonyl-CoA metabolism. These findings support the hypothesis that MCD is a potential therapeutic target for cancer therapy.
    04/2010;
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    ABSTRACT: Our previous reports demonstrated that NAC1, a BTB/POZ domain-containing nuclear protein, upregulates in recurrent ovarian serous carcinoma and participates in developing drug resistance in cancer cells. The current study applies quantitative proteomics to identify the proteins controlled by NAC1 by comparing the proteomes of SKOV3 cells with and without expression of a dominant negative NAC1 construct, N130. From the proteins that are downregulated by N130 (upregulated by NAC1), we chose to further characterize fatty acid synthase (FASN). Similar to change in protein level, the FASN transcript level in SKOV3 cells was significantly reduced by N130 induction or by NAC1 knockdown. Immunohistochemistry showed that NAC1 and FASN immunointensities in ovarian serous carcinoma tissues had a highly significant correlation (P < .0001). Moreover, we found that recurrent serous carcinomas exhibited higher FASN immunointensities than their matched primary tumors (P < .001). Multivariate analysis showed that an FASN staining score of >1 in serous carcinomas was associated with a worse overall survival time (P < .01). Finally, C93, a new FASN inhibitor, induced massive apoptosis in carboplatin/paclitaxel resistant ovarian cancer cells. In conclusion, we show that NAC1 is essential for FASN expression in ovarian serous carcinomas and the expression of FASN significantly correlates with tumor recurrence and disease aggressiveness. The dependence of drug resistant tumor cells on FASN suggests a potential application of FASN-based therapeutics for recurrent ovarian cancer patients.
    Journal of Oncology 01/2010; 2010:285191.
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    ABSTRACT: Fatty acid synthase (FASN) is an emerging tumor-associated marker and a promising antitumor therapeutic target. In this study, we analyzed the expression of FASN in normal and molar placentas, as well as gestational trophoblastic neoplasia, and assessed the effects of a new FASN inhibitor, C93, on cellular proliferation and apoptosis in choriocarcinoma cells. Using a FASN-specific monoclonal antibody, we found that FASN immunoreactivity was detected in the cytotrophoblast and intermediate (extravillous) trophoblast of normal and molar placentas, as well as in placental site nodules. All choriocarcinomas (n = 33), 90% of epithelioid trophoblastic tumors (n = 20), and 60% of placental site trophoblastic tumors (n = 10) exhibited FASN positivity. FASN expression was further confirmed in vitro by Western blot and real-time PCR. Treatment of JEG3 and JAR cells with C93 induced significant apoptosis through the caspase-3/caspase-9/poly(ADP)ribose polymerase pathway. Cell cycle progression was not affected by the inhibitor. In summary, the data indicate that FASN is expressed in the majority of gestational trophoblastic neoplasias, and is essential for choriocarcinoma cells to survive and escape from apoptosis. FASN inhibitors such as C93 warrant further investigation as targeted therapeutic agents for metastatic and chemoresistant gestational trophoblastic neoplasia.
    American Journal Of Pathology 11/2009; 175(6):2618-24. · 4.60 Impact Factor
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    W Zhou, Y Tu, P J Simpson, F P Kuhajda
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    ABSTRACT: Fatty acid synthase (FAS) inhibition initiates selective apoptosis of cancer cells both in vivo and in vitro, which may involve malonyl-CoA metabolism. These findings have led to the exploration of malonyl-CoA decarboxylase (MCD) as a potential novel target for cancer treatment. MCD regulates the levels of cellular malonyl-CoA through the decarboxylation of malonyl-CoA to acetyl-CoA. Malonyl-CoA is both a substrate for FAS and an inhibitor of fatty acid oxidation acting as a metabolic switch between anabolic fatty acid synthesis and catabolic fatty acid oxidation. We now report that the treatment of human breast cancer (MCF7) cells with MCD small interference RNA (siRNA) reduces MCD expression and activity, reduces adenosine triphosphate levels, and is cytotoxic to MCF7 cells, but not to human fibroblasts. In addition, we synthesized a small-molecule inhibitor of MCD, 5-{(Morpholine-4-carbonyl)-[4-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-phenyl]-amino}-pentanoic acid methyl ester (MPA). Similar to MCD siRNA, MPA inhibits MCD activity in MCF7 cells, increases cellular malonyl-CoA levels and is cytotoxic to a number of human breast cancer cell lines in vitro. Taken together, these data indicate that MCD-induced cytotoxicity is likely mediated through malonyl-CoA metabolism. These findings support the hypothesis that MCD is a potential therapeutic target for cancer therapy.
    Oncogene 07/2009; 28(33):2979-87. · 8.56 Impact Factor
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    ABSTRACT: Central and intraperitoneal C75, an inhibitor of fatty acid synthase and stimulator of carnitine palmitoyl-transferase-1, inhibits eating in mice and rats. Mechanisms involved in feeding inhibition after central C75 have been identified, but little is yet known about how systemic C75 might inhibit eating. One issue is whether intraperitoneal C75 reduces food intake in rats by influencing normal physiological controls of food intake or acts nonselectively, for example by eliciting illness or aversion. Another issue relates to whether intraperitoneal C75 acts centrally or, similar to some other peripheral metabolic controls of eating, activates abdominal vagal afferents to inhibit eating. To further address these questions, we investigated the effects of intraperitoneal C75 on spontaneous meal patterns and the formation of conditioned taste aversion (CTA). We also tested whether the eating inhibitory effect of intraperitoneal C75 is vagally mediated by testing rats after either total subdiaphragmatic vagotomy (TVX) or selective subdiaphragmatic vagal deafferentations (SDA). Intraperitoneal injection of 3.2 and 7.5 mg/kg of C75 significantly reduced food intake 3, 12, and 24 h after injection by reducing the number of meals without affecting meal size, whereas 15 mg/kg of C75 reduced both meal number and meal size. The two smaller doses of C75 failed to induce a CTA, but 15 mg/kg C75 did. The eating inhibitory effect of C75 was not diminished in either TVX or SDA rats. We conclude that intraperitoneal injections of low doses of C75 inhibit eating in a behaviorally specific manner and that this effect does not require abdominal vagal afferents.
    AJP Regulatory Integrative and Comparative Physiology 10/2008; 295(3):R799-805. · 3.28 Impact Factor
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    F P Kuhajda
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    ABSTRACT: AMP-activated protein kinase (AMPK) and its upstream kinase, LKB1, act to both monitor and restore cellular energy in response to energy depletion. Studied extensively in liver and skeletal muscle, AMPK is phosphorylated and activated by LKB1 in response to increasing AMP/ATP ratios, which occur in a variety of settings including hypoxia, nutrient starvation and redox imbalance. Interest in the roles of both AMPK and LKB1 in cancer has grown substantially, following the identification of LKB1 as the tumor suppressor gene mutated in the Peutz-Jegher familial cancer syndrome. Patients with the Peutz-Jegher syndrome harbor a single inactive LKB1 gene, and acquisition of a second inactivating lesion (loss of heterozygosity) leads to the development of the cancer in a variety of organs. Thus, the loss of AMPK activation is hypothesized to promote the development of malignancy. Conversely, pharmacological AMPK activation has recently been shown to be cytotoxic to many established human cancer cell lines in vitro and in human cancer xenograft and mouse cancer allografts. Previously, changes in cell metabolism that accompanied the malignant phenotype have largely been considered a consequence of cellular transformation. Now, AMPK and energy metabolism are linked to the development and maintenance of the malignant phenotype. These findings have led to renewed interest in AMPK and cancer cell metabolism in general as potential targets for cancer therapy.
    International journal of obesity (2005) 09/2008; 32 Suppl 4:S36-41. · 5.22 Impact Factor
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    ABSTRACT: Obesity, defined by a body mass index greater than 30kg/m(2), claims an increasing number of lives every year, underscoring a dire need for effective therapeutic interventions. The origins of the obesity epidemic are complex, but commonly cited factors include the large quantities of calorie-rich food that are readily accessible in modern society; eating habits adapted to fast-paced lifestyles; low levels of physical activity; and genetic programs that have evolved, especially in populations prone to famine, to favor the storage of excess calories (i.e., the thrifty-gene theory). It is estimated that more than thirty percent of adults, and about fifteen percent of juveniles, are obese. These high rates have led to dramatic increases in diseases such as type 2 diabetes, cardiovascular and respiratory diseases, depression, and some forms of cancer.
    Molecular Interventions 05/2008; 8(2):82-98. · 6.48 Impact Factor
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    ABSTRACT: Fatty acid synthase (FAS) is overexpressed in lung cancer, and we have investigated the potential use of FAS inhibitors for chemoprevention of lung cancer. Expression of FAS was evaluated in preinvasive human lung lesions (bronchial squamous dysplasia and atypical adenomatous hyperplasia) and in murine models of lung tumorigenesis [4-(methylnitrosamino)-I-(3-pyridyl)-1-butanone-induced and urethane-induced lung tumors in A/J mice]. Then, the ability of pharmacologic inhibitors of FAS to prevent development of the murine tumors was investigated. Finally, the effect of the FAS inhibitor treatment of levels of phosphorylated Akt in the murine tumors was evaluated by immunohistochemistry. Immunohistochemical studies show that human bronchial dysplasia and atypical adenomatous hyperplasia express high levels of FAS compared with normal lung tissues, suggesting that FAS might be a target for intervention in lung carcinogenesis. FAS is also expressed at high levels in chemically induced murine lung tumors, and the numbers and sizes of those murine tumors are significantly reduced by treating carcinogen-exposed mice with pharmacologic inhibitors of FAS, C75 and C93. C93 treatment is associated with reduced levels of phosphorylated Akt in tumor tissues, suggesting that inhibition of this signal transduction pathway might be involved in the chemopreventative activity of this compound. We conclude that increased levels of FAS are common in human preinvasive neoplasia of the lung. Based on studies in mouse models, it seems that inhibiting FAS is an effective strategy in preventing and retarding growth of lung tumors that have high expression of this enzyme.
    Clinical Cancer Research 05/2008; 14(8):2458-64. · 7.84 Impact Factor
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    ABSTRACT: Inhibition of brain carnitine palmitoyl-transferase-1 (CPT-1) is reported to decrease food intake and body weight in rats. Yet, the fatty acid synthase (FAS) inhibitor and CPT-1 stimulator C75 produces hypophagia and weight loss when given to rodents intracerebroventricularly (icv). Thus roles and relative contributions of altered brain CPT-1 activity and fatty acid oxidation in these phenomena remain unclarified. We administered compounds that target FAS or CPT-1 to mice by single icv bolus and examined acute and prolonged effects on feeding and body weight. C75 decreased food intake rapidly and potently at all doses (1-56 nmol) and dose dependently inhibited intake on day 1. Dose-dependent weight loss on day 1 persisted through 4 days of postinjection monitoring. The FAS inhibitor cerulenin produced dose-dependent (560 nmol) hypophagia for 1 day, weight loss for 2 days, and weight regain to vehicle control by day 3. The CPT-1 inhibitor etomoxir (32, 320 nmol) did not alter overall day 1 feeding. However, etomoxir attenuated the hypophagia produced by C75, indicating that CPT-1 stimulation is important for C75's effect. A novel compound, C89b, was characterized in vitro as a selective stimulator of CPT-1 that does not affect fatty acid synthesis. C89b (100, 320 nmol) decreased feeding in mice for 3 days and produced persistent weight loss for 6 days without producing conditioned taste aversion. Similarly, intraperitoneal administration decreased feeding and body weight without producing conditioned taste aversion. These results suggest a role for brain CPT-1 in the regulation of energy balance and implicate CPT-1 stimulation as a pharmacological approach to weight loss.
    AJP Regulatory Integrative and Comparative Physiology 03/2008; 294(2):R352-61. · 3.28 Impact Factor
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    ABSTRACT: Fatty acid synthase (FAS) is overexpressed in many human cancers and is considered to be a promising target for therapy. However, in vitro use of previous generations of FAS inhibitors has been limited by severe, but reversible, anorexia in treated animals, which is thought to be related to a parallel stimulation of fatty acid oxidation by these agents. This study investigated pharmacologic inhibition of FAS using C93, a rationally designed molecule that inhibits FAS activity without affecting fatty acid oxidation in preclinical models of lung cancer. Activity of C93 on FAS and fatty acid oxidation was evaluated in cultured non-small cell lung cancer (NSCLC) cells. Antineoplastic activity of the compound, given orally or by i.p. injection, was evaluated in s.c. and orthotopic NSCLC xenografts. Our experiments confirm that C93 effectively inhibits FAS without stimulating fatty acid oxidation in lung cancer cells. More importantly, C93 significantly inhibits the growth of both s.c. and orthotopic xenograft tumors from human NSCLC cell lines without causing anorexia and weight loss in the treated animals. We conclude that inhibition of FAS can be achieved without parallel stimulation of fatty acid oxidation and that inhibition of tumor growth in vivo can be achieved without anorexia and weight loss. Thus, this therapeutic strategy holds promise for clinical treatment of cancers, including non-small cell lung cancer, the leading cause of cancer mortality in the United States and Europe.
    Clinical Cancer Research 01/2008; 13(23):7139-45. · 7.84 Impact Factor
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    ABSTRACT: Fatty acid synthase (FAS) is an emerging target for anticancer therapy with a variety of new FAS inhibitors being explored in preclinical models. The aim of this study was to use positron emission tomography with [(18)F]fluorodeoxyglucose (FDG-PET) to monitor the effects of the FAS inhibitor C75 on tumor glucose metabolism in a rodent model of human A549 lung cancer. After a baseline FDG-PET scan, C75 was administered and post-treatment scans were performed serially. FAS activity was measured in treated animals ex vivo by [(14)C]acetate incorporation in animals euthanized in parallel to those imaged. Longitudinally measured metabolic volumes of interest and tumor/background ratios demonstrated a transient, reversible decrease in glucose metabolism and tumor metabolic volume after treatment, with the peak effect seen at 4 h. FDG-PET measurements correlated with changes in tumor FAS activity measured ex vivo. Because C75 causes an effect that is shorter in duration than expected, modification of the current weekly dosing regimen should be considered. These results demonstrate the utility of small animal FDG-PET in assessing the pharmacodynamics of new anticancer agents in preclinical models.
    Pharmaceutical Research 06/2007; 24(6):1202-7. · 4.74 Impact Factor
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    ABSTRACT: Fatty acid synthase (FAS), the enzyme responsible for the de novo synthesis of fatty acids, is highly expressed in ovarian cancers and most common human carcinomas. Inhibition of FAS and activation of AMP-activated protein kinase (AMPK) have been shown to be cytotoxic to human cancer cells in vitro and in vivo. In this report, we explore the cytotoxic mechanism of action of FAS inhibition and show that C93, a synthetic FAS inhibitor, increases the AMP/ATP ratio, activating AMPK in SKOV3 human ovarian cancer cells, which leads to cytotoxicity. As a physiologic consequence of AMPK activation, acetyl-CoA carboxylase (ACC), the rate-limiting enzyme of fatty acid synthesis, was phosphorylated and inhibited whereas glucose oxidation was increased. Despite these attempts to conserve energy, the AMP/ATP ratio increased with worsening cellular redox status. Pretreatment of SKOV3 cells with compound C, an AMPK inhibitor, substantially rescued the cells from C93 cytotoxicity, indicating its dependence on AMPK activation. 5-(Tetradecyloxy)-2-furoic acid, an ACC inhibitor, did not activate AMPK despite inhibiting fatty acid synthesis pathway activity and was not significantly cytotoxic to SKOV3 cells. This indicates that substrate accumulation from FAS inhibition triggering AMPK activation, not end-product depletion of fatty acids, is likely responsible for AMPK activation. C93 also exhibited significant antitumor activity and apoptosis against SKOV3 xenografts in athymic mice without significant weight loss or cytotoxicity to proliferating cellular compartments such as bone marrow, gastrointestinal tract, or skin. Thus, pharmacologic FAS inhibition selectively activates AMPK in ovarian cancer cells, inducing cytotoxicity while sparing most normal human tissues from the pleiotropic effects of AMPK activation.
    Cancer Research 05/2007; 67(7):2964-71. · 8.65 Impact Factor
  • Francis P Kuhajda, Gabriele V Ronnett
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    ABSTRACT: The rising incidence of obesity, as a disorder of energy metabolism, has provoked a search for pharmacological agents that either increase energy expenditure or reduce food intake. The fatty acid oxidation pathway, and its rate-limiting enzyme carnitine palmitoyltransferase (CPT)-1 are potential targets for the treatment of obesity. The modulation of CPT-1 may simultaneously affect energy metabolism and food intake to aid in the management of obesity. Both the inhibition and enhancement of CPT-1 activity are currently under investigation as strategies for the treatment of obesity. In this review, key data on both sides of the 'CPT-1 activity balance' as they relate to obesity therapy are discussed.
    Current opinion in investigational drugs (London, England: 2000) 05/2007; 8(4):312-7. · 3.55 Impact Factor
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    ABSTRACT: 3-Carboxy-4-alkyl-2-methylenebutyrolactone (C75), an inhibitor of fatty acid synthase and stimulator of carnitine palmitoyltransferase-1, reduces food intake and body weight in rodents when given systemically or centrally. Intracellular molecular mechanisms involving changes in cellular energy status are proposed to initiate the feeding and body weight reductions. However, effectors that lie downstream of these initial steps are not yet fully identified. Present experiments characterize the time courses of hypophagia and weight loss after single injections of C75 into the lateral cerebroventicle in rats and go on to identify specific meal pattern changes and coinciding alterations in gene expression for feeding-related hypothalamic neuropeptides. C75 reduced chow intake and body weight dose dependently. Although the principal effects occurred on the first day, weight losses relative to vehicle control were maintained over multiple days. C75 did not affect generalized locomotor activity. C75 began to reduce feeding after a 6-h delay. The hypophagia was due primarily to decreased meal number during 6-12 h without a significant effect on meal size, suggesting that central C75 reduced the drive to initiate meals. C75 prevented the anticipated hypophagia-induced increases in mRNA for AgRP in the arcuate nucleus at 22 h and at 6 h when C75 begins to suppress feeding. Overall, the data suggest that gene expression changes leading to altered melanocortin signaling are important for the hypophagic response to intracerebroventricular C75.
    AJP Regulatory Integrative and Comparative Physiology 08/2006; 291(1):R148-54. · 3.28 Impact Factor
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    Francis P Kuhajda
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    ABSTRACT: Fatty acid synthase (FAS), the sole mammalian enzyme capable of de novo fatty acid synthesis, is highly expressed in most human carcinomas. FAS is associated with poor prognosis in breast and prostate cancer, is elaborated into the blood of cancer patients, and its inhibition is selectively cytotoxic to human cancer cells. Thus, FAS and fatty acid metabolism in cancer has become a focus for the potential diagnosis and treatment of cancer.
    Cancer Research 07/2006; 66(12):5977-80. · 8.65 Impact Factor
  • Central Nervous System Agents in Medicinal Chemistry(Formerly Current Medicinal Chemistry - Central Nervous System Agents) 01/2006; 6(1):15-25.
  • Appetite 01/2006; · 2.54 Impact Factor
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    Francis P Kuhajda, Leslie E Landree, Gabriele V Ronnett
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    ABSTRACT: Obesity and its attendant disorders, such as Type II diabetes, have reached epidemic proportions in the USA, and their prevalence is increasing globally. C75 is a small-molecule inhibitor of fatty acid synthase (FAS) and a stimulator of carnitine palmitoyl 1 activity, which causes profound weight loss in mice. Although C75 is not a compound that is destined for human drug development, it has provided two potential pathways to target in obesity therapy: fatty acid synthesis and fatty acid oxidation. In this article, we discuss the latest data challenging the relationship between fatty acid synthase inhibition and C75-induced anorexia.
    Trends in Pharmacological Sciences 12/2005; 26(11):541-4. · 9.25 Impact Factor
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    ABSTRACT: Activation of AKT and overexpression of fatty acid synthase (FAS) are frequently observed in human ovarian cancer. To explore a possible connection between AKT and FAS, immunohistochemical analyses were conducted on an ovarian cancer tissue microarray, which revealed a significant correlation between phosphorylated AKT (phospho-AKT) and expression of FAS. To investigate the relationship between phospho-AKT and FAS in vitro, a variety of experiments employing a specific phosphatidylinositol 3-OH kinase (PI3K) inhibitor (LY294002), inducible PTEN expression in PTEN-null cells, or AKT1 siRNA demonstrated that phosphatidylinositol-3 kinase (PI3K)/AKT signaling modulates FAS expression. In contrast, inhibition of FAS activity by the drug C75 resulted in downregulation of phospho-AKT and increased cell death. To explore the functional relationship between phospho-AKT and FAS, we used SKOV3, C200, and OVCAR10 ovarian carcinoma cells, which have constitutively active AKT, and OVCAR5 cells, which have very low basal phospho-AKT levels. Treatment with LY294002 abolished AKT activity and potentiated apoptosis induced by FAS inhibitors cerulenin or C75 only in cells with constitutively active AKT, suggesting that constitutive activation of AKT protects against FAS inhibitor-induced cell death. Furthermore, inhibition of FAS activity by cerulenin or C75 resulted in downregulation of phospho-AKT, which preceded the induction of apoptosis. To investigate the relationship between phospho-AKT and FAS in vivo, severe combined immunodeficient mice injected intraperitoneally with SKOV3 cells were treated with C75. Growth of SKOV3 xenografts was markedly inhibited by C75. Analysis of the levels of phospho-AKT and FAS in C75-treated tumors revealed concordant downregulation of phospho-AKT and FAS. Collectively, our findings are consistent with a working model in which AKT activation regulates FAS expression, at least in part, whereas FAS activity modulates AKT activation.
    Oncogene 06/2005; 24(22):3574-82. · 8.56 Impact Factor

Publication Stats

5k Citations
545.99 Total Impact Points

Institutions

  • 1987–2011
    • Johns Hopkins University
      • • Department of Pathology
      • • Department of Neuroscience
      • • Department of Biological Chemistry
      • • Department of Medicine
      Baltimore, Maryland, United States
  • 1979–2008
    • Johns Hopkins Medicine
      • • Department of Psychiatry and Behavioral Sciences
      • • Department of Pathology
      Baltimore, MD, United States
  • 1997
    • University of Maryland, Baltimore
      • Department of Pathology
      Baltimore, MD, United States
  • 1985–1988
    • Cornell University
      Ithaca, New York, United States