Akt activation increases cellular cholesterol by promoting the proteasomal degradation of Niemann–Pick C1

2015 ◽  
Vol 471 (2) ◽  
pp. 243-253 ◽  
Author(s):  
Ximing Du ◽  
Yuxi Zhang ◽  
Sae Rom Jo ◽  
Xiaoyun Liu ◽  
Yanfei Qi ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Free Cholesterol ◽  
Cell Signalling ◽  
Proteasomal Degradation ◽  
Active Cell ◽  
Cholesterol Transport ◽  
Cellular Cholesterol ◽  
Akt Activation ◽  
Niemann Pick ◽  
Cell Signalling Pathway

The present study shows that a protein required for proper cholesterol transport in cells is degraded by an active cell signalling pathway. The observations provide new insights into why certain cancer cells have high levels of free cholesterol.

Potential Therapeutic Targets of Curcumin, Most Abundant Active Compound of Turmeric Spice: Role in the Management of Various Types of Cancer

2020 ◽  
Vol 15 ◽  
Author(s):  
Saleh A. Almatroodi ◽  
Mansoor Ali Syed ◽  
Arshad Husain Rahmani
Keyword(s):  
Clinical Trials ◽  
Cancer Cells ◽  
Active Compound ◽  
Molecular Mechanisms ◽  
Human Subjects ◽  
Cell Signalling ◽  
Chemopreventive Agents ◽  
Signalling Molecules ◽  
Cancer Management ◽  
Induced Apoptosis

Background:: Curcumin, an active compound of turmeric spice is one of the most-studies natural compounds and have been widely recognized as chemopreventive agents. Several molecular mechanisms have been proven, curcumin and its analogs play a role in cancer prevention through modulating various cell signaling pathways as well as inhibition of carcinogenesis process. Objective:: To study the potential role of curcumin in the management of various types of cancer through modulating cell signalling molecules based on available literature and recent patents. Methods:: A wide-ranging literature survey was performed based on Scopus, PubMed, PubMed central and Google scholar for the implication of curcumin in cancer management along with special emphasis on human clinical trials. Moreover, patents were searched through www.google.com/patents, www.freepatentsonline.com and www.freshpatents.com. Result:: Recent studies based on cancer cells have proven that curcumin have potential effects against cancer cells, prevent the growth of cancer and act as cancer therapeutic agents. Besides, curcumin exerted anticancer effects through inducing apoptosis, activating tumor suppressor genes, cell cycle arrest, inhibiting tumor angiogenesis, initiation, promotion and progression stages of tumor. It was established that co-treatment of curcumin and anti-cancer drugs could induce apoptosis and also play a significant role in the suppression of the invasion and metastasis of cancer cells. Conclusion:: Accumulating evidences suggest that curcumin has potentiality to inhibit cancer growth, induced apoptosis and modulate various cell signalling pathways molecules. Well-designed clinical trials of curcumin based on human subjects are still needed to establish the bioavailability, mechanism of action, efficacy and safe dose in the management of various cancers.

scholarly journals A new system to evaluate characteristics of Niemann-Pick C1 Like 1-mediated cholesterol transport using Xenopus laevis oocytes

2021 ◽  
Vol 1863 (2) ◽  
pp. 183508
Author(s):  
Shunsuke Nashimoto ◽  
Saori Yagi ◽  
Naoki Takeda ◽  
Miku Nonaka ◽  
Yoh Takekuma ◽  
...  
Keyword(s):  
Xenopus Laevis ◽  
Cholesterol Transport ◽  
Xenopus Laevis Oocytes ◽  
Niemann Pick ◽  
New System

Reverse cholesterol transport: relationship between free cholesterol uptake and HDL3 in normolipidaemic and hyperlipidaemic subjects

1993 ◽  
Vol 23 (2) ◽  
pp. 122-129 ◽  
Author(s):  
M. CASTRO CABEZAS ◽  
G. P. H. VAN HEUSDEN ◽  
T. W. A. DE BRUIN ◽  
J. R. C. M. VAN BECKHOVEN ◽  
L. A. W. KOCK ◽  
...  
Keyword(s):  
Reverse Cholesterol Transport ◽  
Free Cholesterol ◽  
Cholesterol Transport ◽  
Cholesterol Uptake

scholarly journals Use of NBD-cholesterol to identify a minor but NPC1L1-independent cholesterol absorption pathway in mouse intestine

2011 ◽  
Vol 300 (1) ◽  
pp. G164-G169 ◽  
Author(s):  
Michelle R. Adams ◽  
Eddy Konaniah ◽  
James G. Cash ◽  
David Y. Hui
Keyword(s):  
Intestinal Mucosa ◽  
Cholesterol Absorption ◽  
Intestinal Lumen ◽  
Cholesterol Transport ◽  
Cholesteryl Esters ◽  
Main Function ◽  
Absorption Mechanism ◽  
Ezetimibe Treatment ◽  
Niemann Pick ◽  
A Minor

The importance of Niemann-Pick C1 Like-1 (NPC1L1) protein in intestinal absorption of dietary sterols, including both cholesterol and phytosterols, is well documented. However, the exact mechanism by which NPC1L1 facilitates cholesterol transport remains controversial. This study administered 22-( N(-7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-23,24-bisnor-5-cholen-3β-ol (NBD-cholesterol) and [3H]cholesterol to Npc1l1+/+ and Npc1l1−/− mice to determine whether NPC1L1 facilitates dietary sterol uptake by enterocytes and/or participates in intracellular sterol delivery to the endoplasmic reticulum (ER) for lipoprotein assembly before secretion into plasma circulation. Results showed that [3H]cholesterol absorption was reduced but not abolished in Npc1l1−/− mice compared with Npc1l1+/+ mice. In the presence of Pluronic L-81 to block pre-chylomicron exit from the ER, significant amounts of [3H]cholesterol were found to be associated with lipid droplets in the intestinal mucosa of both Npc1l1+/+ and Npc1l1−/− mice, and the intracellular [3H]cholesterol can be esterified to cholesteryl esters. These results provided evidence indicating that the main function of NPC1L1 is to promote cholesterol uptake from the intestinal lumen but that it is not necessary for intracellular cholesterol transport to the ER. Surprisingly, NBD-cholesterol was taken up by intestinal mucosa, esterified to NBD-cholesteryl esters, and transported to plasma circulation to similar extent between Npc1l1+/+ and Npc1l1−/− mice. Ezetimibe treatment also had no impact on NBD-cholesterol absorption by Npc1l1+/+ mice. Thus, NBD-cholesterol absorption proceeds through an NPC1L1-independent and ezetimibe-insensitive sterol absorption mechanism. Taken together, these results indicate that NBD-cholesterol can be used to trace the alternative cholesterol absorption pathway but is not suitable for tracking NPC1L1-mediated cholesterol absorption.

Cell signalling pathway involved in PACAP-induced AR4-2J cell proliferation

1995 ◽  
Vol 7 (3) ◽  
pp. 195-205 ◽  
Author(s):  
Jean Morisset ◽  
Nadine Douziech ◽  
Grazyna Rydzewska ◽  
Louis Buscail ◽  
Nathalie Rivard
Keyword(s):  
Cell Proliferation ◽  
Cell Signalling ◽  
Signalling Pathway ◽  
Cell Signalling Pathway
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