Mitochondrial apoptosis and curtailment of hypoxia‐inducible factor‐1α/fatty acid synthase: A dual edge perspective of gamma linolenic acid in ER+ mammary gland cancer

2020 ◽  
Vol 38 (5) ◽  
pp. 591-603
Author(s):  
Subhadeep Roy ◽  
Manjari Singh ◽  
Atul Rawat ◽  
Dinesh Kumar ◽  
Gaurav Kaithwas
Keyword(s):  
Mammary Gland ◽  
Fatty Acid ◽  
Linolenic Acid ◽  
Fatty Acid Synthase ◽  
Hypoxia Inducible Factor ◽  
Mitochondrial Apoptosis ◽  
Gamma Linolenic Acid ◽  
Hypoxia Inducible Factor 1Α ◽  
Mammary Gland Cancer

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

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.

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

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.

scholarly journals Chemical activation of prolyl hydroxylase-2 by BBAP-1 down regulates hypoxia inducible factor-1α and fatty acid synthase for mammary gland chemoprevention

RSC Advances ◽  
2018 ◽  
Vol 8 (23) ◽  
pp. 12848-12860 ◽  
Author(s):  
Manjari Singh ◽  
Uma Devi ◽  
Subhadeep Roy ◽  
Pushpraj S. Gupta ◽  
Gaurav Kaithwas
Keyword(s):  
Mammary Gland ◽  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Chemical Activation ◽  
Hypoxia Inducible Factor ◽  
Prolyl Hydroxylase ◽  
Phenyl Acetate ◽  
Hypoxia Inducible Factor 1Α

(4-[7-(Acetyloxy)-2-ethyl-2H-chromen-3-yl] phenyl acetate) (BBAP-1) was identified as a potential prolyl hydroxylase-2 activator and tested for this activity using the 2-oxoglutarate dependentin vitroassay.

scholarly journals Repurposing Combination Therapy of Voacamine With Vincristine for Downregulation of Hypoxia-Inducible Factor-1α/Fatty Acid Synthase Co-axis and Prolyl Hydroxylase-2 Activation in ER+ Mammary Neoplasia

2021 ◽  
Vol 9 ◽  
Author(s):  
Lakhveer Singh ◽  
Subhadeep Roy ◽  
Anurag Kumar ◽  
Shubham Rastogi ◽  
Dinesh Kumar ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Tumor Microenvironment ◽  
Fatty Acid Synthesis ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Hypoxia Inducible Factor ◽  
Acid Synthesis ◽  
Prolyl Hydroxylase ◽  
Proliferating Cells ◽  
Hypoxia Inducible Factor 1Α

Graphical AbstractMechanism of VOA and VIN to inhibit fatty acid synthesis in DMBA-induced mammary gland carcinoma of albino Wistar rats. Hypoxia-activated HIF-1α enhances lactate acidosis in the tumor microenvironment, and dysregulated pH in the tumor microenvironment activates SREBP-1c and FASN expression to speed up the fatty acid synthesis required for plasma membrane synthesis in rapidly proliferating cells. VOA- and VIN-activated PHD-2 enhanced the proteolytic degradation of HIF, thus inhibiting fatty acid synthesis. HIF-1α, hypoxia-inducible factor-1α; SREBP-1c, sterol regulatory element-binding protein-1c; FASN, fatty acid synthesis; PHD-2, prolyl hydroxylase-2.

scholarly journals Hypoxia-inducible Factor-1α Induces ErbB4 Signaling in the Differentiating Mammary Gland

2014 ◽  
Vol 289 (32) ◽  
pp. 22459-22469 ◽  
Author(s):  
Ilkka Paatero ◽  
Tiffany N. Seagroves ◽  
Katri Vaparanta ◽  
Wen Han ◽  
Frank E. Jones ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1Α

scholarly journals Regulation of lipogenic capacity in lactating rats

1982 ◽  
Vol 208 (3) ◽  
pp. 611-618 ◽  
Author(s):  
M R Grigor ◽  
A Geursen ◽  
M J Sneyd ◽  
S M Warren
Keyword(s):  
Mammary Gland ◽  
Fatty Acid ◽  
Malic Enzyme ◽  
Fatty Acid Synthase ◽  
Specific Activity ◽  
Mammary Glands ◽  
Lipogenic Enzymes ◽  
Pregnancy And Lactation ◽  
Specific Activities

1. The rate of mammary-gland lipogenesis measured in vivo from 3H2O was suppressed after decreasing the milk demand by decreasing the number of pups from ten to two or three, as well as by giving diets containing lipid [Grigor & Warren (1980) Biochem. J. 188, 61-65]. 2. The specific activities of the lipogenic enzymes fatty acid synthase, glucose 6-phosphate dehydrogenase and ‘malic’ enzyme increased between 6- and 10-fold in the mammary gland and between 2- and 3-fold in the livers during the first 10 days of lactation. The increases in specific activity coupled with the doubling of liver mass which occurred during pregnancy and lactation resulted in considerable differences in total liver activities when compared with virgin animals. 3. Although consumption of a diet containing 20% peanut oil suppressed the activities of the three lipogenic enzymes in the livers, only the ‘malic’ enzyme was affected in the mammary glands. 4. In contrast, decreased milk demand did not affect the specific activities of any of the liver enzymes, whereas it resulted in suppression of all three lipogenic enzymes of the mammary glands. There was no effect on either the cytoplasmic malate dehydrogenase or the lactate dehydrogenase of the mammary gland. 5. In all the experiments performed, the activity of the fatty acid synthase correlated with the amount of material precipitated by the rabbit antibody raised against rat fatty acid synthase.

Gamolenic acid in atopic eczema: ▾ epogam

1990 ◽  
Vol 28 (18) ◽  
pp. 69-70
Keyword(s):  
Fatty Acid ◽  
Linoleic Acid ◽  
Linolenic Acid ◽  
Essential Fatty Acid ◽  
Atopic Eczema ◽  
Conventional Treatment ◽  
Gamma Linolenic Acid ◽  
Evening Primrose

Epogam capsules (Scotia) contain oil from the seed of the evening primrose which is rich in the essential fatty acid linoleic acid and its metabolite gamolenic (gamma-linolenic) acid. Epogam is licensed for use to relieve symptoms in atopic eczema, and is claimed to act at a fundamental metabolic level in this disease. Conventional treatment of eczema is often unsatisfactory, and any claim of an advance must be taken seriously. How well founded are the claims made for Epogam?

scholarly journals Rat mammary-gland fatty acid synthase. A simple purification procedure and stoicheiometry of CoA ester binding

1982 ◽  
Vol 203 (1) ◽  
pp. 45-50 ◽  
Author(s):  
P M Ahmad ◽  
D S Feltman ◽  
F Ahmad
Keyword(s):  
Mammary Gland ◽  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Specific Activity ◽  
Simple Procedure ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Performic Acid ◽  
Mammary Tissue ◽  
Rat Mammary Gland

A simple procedure was devised which allows purification of rat lactating-mammary-gland fatty acid synthase to a high degree of purity, with recoveries of activity exceeding 50%. Over 50 mg of enzyme was isolated from 60 g of mammary tissue. The specific activity of the purified enzyme was about 2.5 mumol of NADPH oxidized/min per mg of protein at 37 degrees. The enzyme appeared homogeneous by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis and by immunodiffusion analysis. Each mol (Mr 480 000) of the enzyme bound 3 mol of acetyl and 3-4 mol of malonyl groups when the binding experiments were performed at 0 degrees for 30 s. The presence of NADPH did not influence the binding stoicheiometry for these acyl-CoA derivatives. Approx. 2 mol of taurine was found per mol of the performic acid-oxidized enzyme, suggesting that there were 2 mol of 4′-phosphopantetheine in the native enzyme. Rat mammary-gland fatty acid synthase required free CoA for activity.

Fungal Production of Omega-6 Fatty Acid: Gamma-Linolenic Acid

2007 ◽  
Vol 1 (2) ◽  
pp. 127-130 ◽  
Author(s):  
N. Rajendra Goud ◽  
Ujjwal Neogi . ◽  
Ruchi Saumya .
Keyword(s):  
Fatty Acid ◽  
Linolenic Acid ◽  
Gamma Linolenic Acid ◽  
Omega 6
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