Role of Cytochrome P450 in Prostate Cancer and its Therapy

2020 ◽  
Vol 16 (1) ◽  
pp. 63-73 ◽  
Author(s):  
Rishabh Kaushik ◽  
Sheeza Khan ◽  
Meesha Sharma ◽  
Srinivasan Hemalatha ◽  
Zeba Mueed ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cytochrome P450 ◽  
Drug Discovery ◽  
Cholesterol Metabolism ◽  
Molecular Targets ◽  
Health Concern ◽  
Metabolic Functions ◽  
Novel Drugs ◽  
Genes Encoding ◽  
Causes Of Mortality

Prostate cancer has become a global health concern as it is one of the leading causes of mortality in males. With the emerging drug resistance to conventional therapies, it is imperative to unravel new molecular targets for disease prevention. Cytochrome P450 (P450s or CYPs) represents a unique class of mixed-function oxidases which catalyses a wide array of biosynthetic and metabolic functions including steroidogenesis and cholesterol metabolism. Several studies have reported the overexpression of the genes encoding CYPs in prostate cancer cells and how they can be used as molecular targets for drug discovery. But due to functional redundancy and overlapping expression of CYPs in several other metabolic pathways there are several impediments in the clinical efficacy of the novel drugs reported till now. Here we review the most crucial P450 enzymes which are involved in prostate cancer and how they can be used as molecular targets for drug discovery along with the clinical limitations of the currently existing CYP inhibitors.

scholarly journals Association of CYP1A1, GSTM1 and GSTT1 gene polymorphisms with risk of prostate cancer in Algerian population

2020 ◽  
Vol 26 (1) ◽  
Author(s):  
Somia Medjani ◽  
Djalila Chellat-Rezgoune ◽  
Taher Kezai ◽  
Mohammed Chidekh ◽  
Noureddine Abadi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Susceptibility ◽  
Prostate Cancer Risk ◽  
Detoxification Enzymes ◽  
Current Case ◽  
Algerian Population ◽  
Pcr Rflp ◽  
Genes Encoding ◽  
Genetic And Environmental Factors ◽  
Metabolism Of Xenobiotics

Abstract Background Prostate cancer is the most common cancer in the world, and its etiology involves the interaction of genetic and environmental factors. Interindividual differences observed in the metabolism of xenobiotics may be due to polymorphisms of genes encoding the detoxification enzymes. This genetic variability seems to be associated with differences in susceptibility to certain types of cancers, including prostate cancer. Our study has been made in order to investigate a possible genetic predisposition to prostate cancer in an Algerian population, through the analysis of genetic polymorphisms of three enzymes metabolizing xenobiotics namely cytochrome P450 (CYP) 1A1, glutathione S-transferase mu 1 (GSTM1) and GST theta 1 (GSTT1). Methods The current case–control study included 101 prostate cancer patients and 101 healthy controls. Genotyping of CYP1A1 T3801C polymorphisms and GSTM1/GSTT-null was made, respectively, by PCR-RFLP and multiplex PCR. Results No significantly positive associations were found for the CYP1A1 T3801C [p = 0.71, OR = 1.23 (0.56–2.72)] and GSTM1-null [p = 0.26, OR = 1.37 (0.76–2.4)] polymorphisms and prostate cancer susceptibility. However, we detect a highly significant association between GSTT1-null genotype [p = 0.03, OR = 2.03 (1.06–3.99)], GSTM1/GSTT1-double null genotype [p = 0.027, OR = 2.6; CI (1.07–6.5)] and prostate cancer risk. Furthermore, no statistically significant differences between the studied polymorphisms and tumor parameters (the Gleason score and clinical stages of aggressiveness) at diagnosis of PCa. Conclusions The risk of developing prostate cancer in Algeria does not appear to be associated with CYP1A1 T3801C genotypes and GSTM1-null, but GSTT1-null and GSTM1/GSTT1-double null genotypes increased the risk of prostate cancer.

The roles of amino acid residues at positions 216 and 219 in the structural stability and metabolic functions of rat cytochrome P450 2D1 and 2D2

2008 ◽  
Vol 172 (1) ◽  
pp. 11-21 ◽  
Author(s):  
Shizuo Narimatsu ◽  
Kimio Kiryu ◽  
Rei Yonemoto ◽  
Manabu Yoshino ◽  
Mitsuko Kobatake ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Amino Acid ◽  
Structural Stability ◽  
Amino Acid Residues ◽  
Metabolic Functions

Abstract 162: Cholesterol metabolism gene expression and prostate cancer-specific outcomes in radiotherapy-treated patients

2021 ◽  
Author(s):  
Sarah J. Winter ◽  
Sophia Halliday ◽  
Konrad H. Stopsack ◽  
Sarah O. Osman ◽  
Alan R. Hounsell ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Cholesterol Metabolism ◽  
Metabolism Gene

scholarly journals American trends in expectant management utilization for prostate cancer from 2000 to 2009

2014 ◽  
Vol 8 (11-12) ◽  
pp. 775 ◽  
Author(s):  
Matthew J. Maurice ◽  
Robert Abouassaly ◽  
Hui Zhu
Keyword(s):  
Prostate Cancer ◽  
Expectant Management ◽  
Patient Characteristics ◽  
Veterans Affairs ◽  
Health Concern ◽  
Teaching Hospitals ◽  
Limited Life ◽  
Appreciable Increase ◽  
Low Volume

Introduction: The overtreatment of early prostate cancer has become a major public health concern. Expectant management (EM) is a strategy to minimize overtreatment, but little is known about its pattern of use. We sought to examine national EM utilization over the preceding decade.Methods: We examined prostate cancer treatment utilization from 2000 to 2009 using the National Cancer Database. EM use was analyzed in relation to other treatments and by cancer stage, age group, Charlson score, and hospital practice setting.Results: Overall, 109 997 (8.2%) men were managed initially with EM. EM usage remained stable at 7.6% to 9.5% from 2000 to 2009 with no appreciable increase for low-stage cancers. Usage was only slightly higher in elderly patients and in patients with multiple comorbidities. Veterans Affairs and low-volume hospitals had a much higher and increasing EM rate (range: 18.8%-29.8% and 15.1%-24.2%, respectively), compared to community hospitals, comprehensive cancer centres, and teaching hospitals, which showed no increased adoption. On further analysis, EM use remained high for low-stage cancers at Veterans Affairs and low-volume hospitals (24.0% and 19.1%, respectively), regardless of age or comorbidity, a pattern not shared by other practice settings.Conclusions: EM utilization remained low and stable last decade, regardless of disease or patient characteristics. Conversely, Veterans Affairs and low-volume hospitals led the trend in national EM adoption, particularly in men with low-stage cancers and limited life expectancies. The limitations of this dataset preclude any determination of the appropriateness of EM utilization. Nonetheless, further study is needed to identify factors influencing EM adoption to ensure its proper use in the future.

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