Antiangiogenics and Hypoxic Response: Role of Fatty Acid Synthase Inhibitors

Transcription of fatty acid synthase (FAS) and malic enzyme (ME) in avian liver is low during starvation or feeding a low-carbohydrate, high-fat diet and high during feeding a high-carbohydrate, low-fat diet. The role of glucose in the nutritional control of FAS and ME was investigated by determining the effects of this metabolic fuel on expression of FAS and ME in primary cultures of chick embryo hepatocytes. In the presence of triiodothyronine, glucose (25 mM) stimulated an increase in the activity and mRNA abundance of FAS and ME. These effects required the phosphorylation of glucose to glucose 6-phosphate but not further metabolism downstream of the aldolase step of the glycolytic pathway. Xylitol mimicked the effects of glucose on FAS and ME expression, suggesting that an intermediate of the pentose phosphate pathway may be involved in mediating this response. The effects of glucose on the mRNA abundance of FAS and ME were accompanied by similar changes in transcription of FAS and ME. These data support the hypothesis that glucose plays a role in mediating the effects of nutritional manipulation on transcription of FAS and ME in liver.

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Emerging role of Fatty acid synthase in tumor initiation: implications for cancer prevention

Molecular & Cellular Oncology ◽

10.1080/23723556.2019.1709389 ◽

2020 ◽

Vol 7 (2) ◽

pp. 1709389 ◽

Cited By ~ 1

Author(s):

Maria J. Bueno ◽

Miguel Quintela-Fandino

Keyword(s):

Fatty Acid ◽

Cancer Prevention ◽

Fatty Acid Synthase ◽

Tumor Initiation

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Sa1466 Obesity, Gender and Colorectal Carcinogenesis: Role of Fatty Acid Synthase

Gastroenterology ◽

10.1016/s0016-5085(12)61173-1 ◽

2012 ◽

Vol 142 (5) ◽

pp. S-313 ◽

Cited By ~ 1

Author(s):

Mart DeLaCruz ◽

Dhananjay Kunte ◽

Boris Jancan ◽

Nela Krosnjar ◽

Tina P. Gibson ◽

...

Keyword(s):

Fatty Acid ◽

Fatty Acid Synthase ◽

Colorectal Carcinogenesis

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Repurposing combination therapy of Voacamine with Vincristine for down regulation of HIF-1α/FASN co-axis and PHD2 activation in ER+ mammary neoplasia

10.21203/rs.3.rs-61541/v1 ◽

2020 ◽

Author(s):

Lakhveer Singh ◽

Manjari Singh ◽

Dinesh Kumar ◽

Mohd. Nazam Ansari ◽

Abdulaziz S. Saeedan ◽

...

Keyword(s):

Mammary Gland ◽

Fatty Acid ◽

Combination Therapy ◽

Fatty Acid Synthase ◽

Hypoxia Inducible Factor ◽

Prolyl Hydroxylase ◽

Over Expression ◽

Hypoxia Inducible Factor 1Α ◽

Gland Carcinoma

Abstract Background The current study was attempted to inquest the role of combination therapy of Voacamine and Vincristine for the prevention of mammary gland carcinoma through prolyl hydroxylase-2 activation. The prolyl hydroxylase‐2 activation leads the downregulation of hypoxia‐inducible factor‐1α and fatty acid synthase. Over expression of hypoxia inducible factor-1α and fatty acid synthase is previously reported in solid tumor of mammary gland. Methods After screening a battery of natural compounds which were similar to vincristine, vocamine was selected as a possible prolyl hydroxylase-2 activator and justify its activity using 7, 12-Dimethylbenz[a]anthracene induced rat model. The combination therapy was evaluated for cardiac toxicity using hemodynamic profile. The angiogenic markers were evaluated using carmine staining. Monotherapy and combination therapy were also evaluated for liver and kidney toxicity through haematoxylin and eosin staining. The combination therapy also delineated the markers of oxidative stress favorably. Afterwards, the disruption of fatty acids was evaluated using gas chromatography. Results The immunoblotting analysis validated that combination therapy has a potential to switch on the prolyl hydroxylase-2 activity and thus initiate proteolytic degradation of hypoxia‐inducible factor‐1α and its consequence effects. The combination therapy also stimulated programmed cell death (apoptosis) in rapidly dividing cancer cells. Conclusion The present study explores the role of voacamine in activation of prolyl hydroxylase-2 which can decrease over expression of hypoxia‐inducible factor‐1α and fatty acid synthase in cells of mammary gland carcinoma.

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Repurposing Combination Therapy of Voacamine with Vincristine for Down Regulation of HIF-1α/FASN Co-Axis and PHD2 Activation in ER+ Mammary Neoplasia

10.21203/rs.3.rs-34012/v1 ◽

2020 ◽

Author(s):

Lakhveer Singh ◽

Manjari Singh ◽

Mohd. Nazam Ansari ◽

Abdulaziz S. Saeedan ◽

Gaurav Kaithwas

Keyword(s):

Mammary Gland ◽

Fatty Acid ◽

Combination Therapy ◽

Fatty Acid Synthase ◽

Hypoxia Inducible Factor ◽

Prolyl Hydroxylase ◽

Over Expression ◽

Hypoxia Inducible Factor 1Α ◽

Gland Carcinoma

Abstract Background: The current study was attempted to inquest the role of combination therapy of Voacamine and Vincristine for the prevention of mammary gland carcinoma through prolyl hydroxylase‐2 activation. The prolyl hydroxylase‐2 activation leads the downregulation of hypoxia‐inducible factor‐1α and fatty acid synthase. Over expression of hypoxia inducible factor-1α and fatty acid synthase is previously reported in solid tumor of mammary gland. Methods: After screening a battery of natural compounds which were similar to vincristine, vocamine was selected as a possible prolyl hydroxylase‐2 activator and justify its activity using 7, 12-Dimethylbenz[a]anthracene induced rat model. The combination therapy was evaluated for cardiac toxicity using hemodynamic profile. The angiogenic markers were evaluated using carmine staining. Monotherapy and combination therapy were also evaluated for liver and kidney toxicity through haematoxylin and eosin staining. The combination therapy also delineated the markers of oxidative stress favorably. Afterwards, the disruption of fatty acids was evaluated using gas chromatography. Results: The immunoblotting analysis validated that combination therapy has a potential to switch on the prolyl hydroxylase‐2 activity and thus initiate proteolytic degradation of hypoxia‐inducible factor‐1α and its consequence effects. The combination therapy also stimulated programmed cell death (apoptosis) in rapidly dividing cancer cells.Conclusion: The present study explores the role of voacamine in activation of prolyl hydroxylase‐2 which can decrease over expression of hypoxia‐inducible factor‐1α and fatty acid synthase in cells of mammary gland carcinoma.

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Fatty acid synthase is a prognostic marker and associated with immune infiltrating in gastric cancers precision medicine

Biomarkers in Medicine ◽

10.2217/bmm-2019-0476 ◽

2020 ◽

Vol 14 (3) ◽

pp. 185-199

Author(s):

Yangying Zhou ◽

Weiping Su ◽

Huan Liu ◽

Taili Chen ◽

Naseruddin Höti ◽

...

Keyword(s):

Gastric Cancer ◽

Fatty Acid ◽

Fatty Acid Synthase ◽

De Novo ◽

Survival Outcome ◽

De Novo Synthesis ◽

Bioinformatics Analyses ◽

Key Enzyme ◽

Tumor Types

Aim: Fatty acid synthase (FASN), a key enzyme for de novo synthesis of fatty acids, has been identified as an oncogene in some tumor types; however, the function of FASN in gastric cancer (GC) is poorly elucidated. Method: Integrative bioinformatics analyses were performed to unveil the role of FASN in tumor progression and cancer-associated immunology of GC. Result: FASN was overexpressed in the GC tissues and correlated with an inferior survival outcome, and largely contributed to the carcinogenesis of GC. Moreover, FASN expression was closely associated with the immune-infiltrating levels of CD8+ T, CD4+ T, neutrophils, macrophages and dendritic cells. Conclusion: FASN was closely associated with GC and may be involved in the tumorigenesis and cancer–immune interactions, and could be a promising prognostic and therapeutic biomarker in GC.

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Analysis of the Expression of Genes Related to Lipidic and Glycogenic Metabolism in Pleomorphic Adenomas and Carcinomas Ex Pleomorphic Adenomas

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqz126.004 ◽

2019 ◽

Vol 152 (Supplement_1) ◽

pp. S135-S136

Author(s):

Erika Egal ◽

Joao Scarini ◽

Larissa Fernandes ◽

Welligton Sabino ◽

Reydson Souza ◽

...

Keyword(s):

Gene Expression ◽

Fatty Acid ◽

Pleomorphic Adenoma ◽

Malignant Transformation ◽

Fatty Acid Synthase ◽

Carcinoma Ex Pleomorphic Adenoma ◽

Glut 1 ◽

Significant Difference ◽

Pleomorphic Adenomas

Abstract Introduction The carcinoma ex pleomorphic adenoma (CXPA) arises from a pleomorphic adenoma (PA) and is supposed to gain lipogenesis and glycogenesis during its malignant transformation. Increased lipogenesis is a characteristic of cancer cells, consisting of increased fatty acid synthesis by the enzyme fatty acid synthase (FASN) and by the accumulation of cytoplasmic lipid droplets, which express adipophilin. The increase in glycolytic metabolism has been associated with the activity of glycolytic enzymes and glucose transporters (GLUTs), whose expression is induced by HIF-1 (inducing factor of hypoxia 1). Objectives To analyze the gene expression of FASN, adipophilin, HIF-1α, and GLUT-1 in PA and CXPA samples. Methodology Gene expression analysis of the FASN, adipophilin, HIF1-α, and GLUT-1 genes was performed by the real-time PCR (qPCR) method. Fourteen cases of PA and 14 cases of CXAP were evaluated. Results FASN, adipophilin, HIF-1α, and GLUT-1 were more expressed in CXAP than in AP, although there was no significant difference between levels of adipophilin expression in CXPA and PA. Conclusion Increased expression of FASN, HIF1-α, and GLUT-1 in CXAP may be associated with malignant transformation of PA, while additional studies are needed to understand the role of adipophilin in PA carcinogenesis. Moreover, this is the first study to investigate the role of these genes in the malignant transformation of PA.

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