title: Prolyl hydroxylase mediated inhibition of fatty acid synthase to combat tumor growth in mammary gland carcinoma.
abstract: Cancer is a group of cells which grow in an uncontrolled manner and invades to the adjacent organs to form malignant tumors. Tumor hypoxia results due to contrast between the cellular oxygen expenditure and oxygen supply to the cells. Hypoxia inducible factor (HIF) is a heterodimeric transcription factor encompass of oxygen sensitive α subunit and constitutively expressed β subunit both of which are basic helix-loop-helix protein. The stability of HIF is primarily regulated by post translational prolyl hydroxylation, catalyzed by prolyl hydroxylase 2 (Phd-2). Phd-2 is a group of enzymes that acts as an oxygen sensor. Cancer cells have altered metabolism as they fulfil their energy needs through glycolysis and lipid biogenesis. HIF-1α is known to upregulate glycolysis by activating the transcription of enzymes on the glycolytic pathway and through lipogenesis. Cancer cells have over expressed fatty acid synthase owing to altered glycolytic pathway. Considering the above, it is hypothesized that chemical activation of Phd-2 can curtail down HIF-1α and subsequently fatty acid synthase expression.
authors.affiliation: Department of Pharmaceutical Sciences, School of Biosciences and Biotechnology, Babasaheb Bhimrao Ambedkar University (A Central University), Vidya Vihar, Raebareli Road, Lucknow, 226025, India.
authors.forename: Manjari
authors.initials: M
authors.lastname: Singh
authors.affiliation: Department of Pharmaceutical Sciences, Faculty of Health Medical Sciences Indigenous and Alternative Medicine, SHIATS-Deemed to be University, Naini, Allahabad, Uttar Pradesh, India.
authors.forename: Uma
authors.initials: U
authors.lastname: Devi
authors.affiliation: Department of Pharmaceutical Sciences, School of Biosciences and Biotechnology, Babasaheb Bhimrao Ambedkar University (A Central University), Vidya Vihar, Raebareli Road, Lucknow, 226025, India.
authors.forename: Subhadeep
authors.initials: S
authors.lastname: Roy
authors.affiliation: Department of Pharmaceutical Sciences, Faculty of Health Medical Sciences Indigenous and Alternative Medicine, SHIATS-Deemed to be University, Naini, Allahabad, Uttar Pradesh, India.
authors.forename: Pushpraj S
authors.initials: PS
authors.lastname: Gupta
authors.affiliation: Department of Pharmaceutical Sciences, School of Biosciences and Biotechnology, Babasaheb Bhimrao Ambedkar University (A Central University), Vidya Vihar, Raebareli Road, Lucknow, 226025, India.
authors.forename: Shubhini A
authors.initials: SA
authors.lastname: Saraf
authors.affiliation: Department of Pharmaceutical Sciences, School of Biosciences and Biotechnology, Babasaheb Bhimrao Ambedkar University (A Central University), Vidya Vihar, Raebareli Road, Lucknow, 226025, India. gauravpharm@gmail.com.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Kaithwas
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015687:Cell Hypoxia; D054890:Fatty Acid Synthase, Type I / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases / Q000378:metabolism*; D059016:Tumor Microenvironment
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C490190:EGLN1 protein, human; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I
keywords: Fatty acid synthase; Hypoxia; Hypoxia inducible factor; Normoxia; Prolyl hydoxylase