Cognition, Age, and RaPamycin Effectiveness - DownregulatIon of thE mTor Pathway

This study aimed to investigate the mechanism of betulinic acid on multiple myeloma cell resistance to bortezomib. To this end, the bortezomib-resistant RPMI-8226-R cells were generated by prolonged treatment of RPMI-8226 cells with increasing concentrations of bortezomib. Based on the measurements of cell viability and colony number, RPMI-8226-R cells exhibited enhanced resistance to bortezomib than RPMI-8226 cells. Treatment with betulinic acid resulted in increased sensitivity of RPMI-8226-R to bortezomib. When RPMI-8226-R cells were co-treated with bortezomib and betulinic acid, there was an increase in apoptosis rate, cleaved caspase-3, cleaved caspase-9 expression and the decrease in p-AKT/AKT and p-mTOR/mTOR levels. These results suggest that betulinic acid enhances the sensitivity of RPMI-8226-R cells to bortezomib by inhibiting the activation of the AKT/mTOR pathway in bortezomib-resistant multiple myeloma cells.

Download Full-text

Chitosan Oligosaccharides Inhibit Tumor Progression and Induce Autophagy Through Activation of the p53/mTOR Pathway in Osteosarcoma

SSRN Electronic Journal ◽

10.2139/ssrn.3457401 ◽

2019 ◽

Author(s):

Zhen Pan ◽

Xiao-juan Wei ◽

Shi-jie Li ◽

Hua Guo ◽

Dong-dong Cheng ◽

...

Keyword(s):

Tumor Progression ◽

Mtor Pathway ◽

Chitosan Oligosaccharides

Download Full-text

Targeting mammalian target of rapamycin: prospects for the treatment of inflammatory bowel diseases

Current Medicinal Chemistry ◽

10.2174/0929867327666200504081503 ◽

2020 ◽

Vol 27 ◽

Author(s):

Naser-Aldin Lashgari ◽

Nazanin Momeni Roudsari ◽

Saeideh Momtaz ◽

Negar Ghanaatian ◽

Parichehr Kohansal ◽

...

Keyword(s):

Signaling Pathway ◽

Mammalian Target Of Rapamycin ◽

Mtor Pathway ◽

Mtor Signaling ◽

Target Of Rapamycin ◽

In Vivo Studies ◽

Cochrane Library ◽

Mtor Signaling Pathway ◽

Inflammatory Bowel

: Inflammatory bowel disease (IBD) is a general term for a group of chronic and progressive disorders. Several cellular and biomolecular pathways are implicated in the pathogenesis of IBD, yet the etiology is unclear. Activation of the mammalian target of rapamycin (mTOR) pathway in the intestinal epithelial cells was also shown to induce inflammation. This review focuses on the inhibition of the mTOR signaling pathway and its potential application in treating IBD. We also provide an overview on plant-derived compounds that are beneficial for the IBD management through modulation of the mTOR pathway. Data were extracted from clinical, in vitro and in vivo studies published in English between 1995 and May 2019, which were collected from PubMed, Google Scholar, Scopus and Cochrane library databases. Results of various studies implied that inhibition of the mTOR signaling pathway downregulates the inflammatory processes and cytokines involved in IBD. In this context, a number of natural products might reverse the pathological features of the disease. Furthermore, mTOR provides a novel drug target for IBD. Comprehensive clinical studies are required to confirm the efficacy of mTOR inhibitors in treating IBD.

Download Full-text

PI3K/ Akt/ mTOR Pathway as a Therapeutic Target for Colorectal Cancer: A Review of Preclinical and Clinical Evidence

Current Drug Targets ◽

10.2174/1389450120666190618123846 ◽

2019 ◽

Vol 20 (12) ◽

pp. 1217-1226 ◽

Cited By ~ 14

Author(s):

Arunaksharan Narayanankutty

Keyword(s):

Colorectal Cancer ◽

Drug Resistance ◽

Therapeutic Target ◽

Clinical Evidence ◽

Mtor Pathway ◽

Colorectal Cancers ◽

Patent Literature ◽

Mtor Signalling ◽

Natural And Synthetic

Background: Phosphoinositide 3-kinase (PI3Ks) is a member of intracellular lipid kinases and involved in the regulation of cellular proliferation, differentiation and survival. Overexpression of the PI3K/Akt/mTOR signalling has been reported in various forms of cancers, especially in colorectal cancers (CRC). Due to their significant roles in the initiation and progression events of colorectal cancer, they are recognized as a striking therapeutic target. Objective: The present review is aimed to provide a detailed outline on the role of PI3K/Akt/mTOR pathway in the initiation and progression events of colorectal cancers as well as its function in drug resistance. Further, the role of PI3K/Akt/mTOR inhibitors alone and in combination with other chemotherapeutic drugs, in alleviating colorectal cancer is also discussed. The review contains preclinical and clinical evidence as well as patent literature of the pathway inhibitors which are natural and synthetic in origin. Methods: The data were obtained from PubMed/Medline databases, Scopus and Google patent literature. Results: PI3K/Akt/mTOR signalling is an important event in colorectal carcinogenesis. In addition, it plays significant roles in acquiring drug resistance as well as metastatic initiation events of CRCs. Several small molecules of natural and synthetic origin have been found to be potent inhibitors of CRCs by effectively downregulating the pathway. Data from various clinical studies also support these pathway inhibitors and several among them are patented. Conclusion: Inhibitors of the PI3K/mTOR pathway have been successful for the treatment of primary and metastatic colorectal cancers, rendering the pathway as a promising clinical cancer therapeutic target.

Download Full-text

The Novel VEGF121-VEGF165 Fusion Attenuates Angiogenesis and Drug Resistance via Targeting VEGFR2-HIF-1α-VEGF165/Lon Signaling Through PI3K-AKT-mTOR Pathway

Current Cancer Drug Targets ◽

10.2174/156800961603160206125352 ◽

2016 ◽

Vol 16 (3) ◽

pp. 275-286 ◽

Cited By ~ 6

Author(s):

Jui-Ling Tsai ◽

Yu-May Lee ◽

Chien-Yuan Pan ◽

Alan Yueh-Luen Lee

Keyword(s):

Drug Resistance ◽

Mtor Pathway ◽

The Novel

Download Full-text

Apoptotic Effects of Xanthium strumarium via PI3K/AKT/mTOR Pathway in Hepatocellular Carcinoma

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/2176701 ◽

2019 ◽

Vol 2019 ◽

pp. 1-13

Author(s):

Juyoung Kim ◽

Kyung Hee Jung ◽

Hyung Won Ryu ◽

Doo-Young Kim ◽

Sei-Ryang Oh ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Growth ◽

Caspase 3 ◽

Mtor Pathway ◽

Terminal Deoxynucleotidyl Transferase ◽

Mechanistic Study ◽

Migration And Invasion ◽

Xanthium Strumarium ◽

Apoptotic Effects ◽

Hcc Cells

Xanthium strumarium (XS) has been traditionally used as a medicinal herb for treating inflammatory diseases, such as appendicitis, chronic bronchitis, rheumatism, and rhinitis. In this study, we yielded ethanol extracts from XS and investigated whether they could inhibit the progression of hepatocellular carcinoma (HCC) and its underlying mechanism. The XS-5 and XS-6 extracts dose-dependently inhibited the growth and proliferation in HCC cell lines. The apoptotic effects of them were observed via increased levels of cleaved caspase-3 and cleaved PARP, as well as elevated numbers of terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling- (TUNEL-) positive apoptotic cells. They also decreased XIAP and Mcl-1 expression via loss of mitochondrial membrane potential. Additionally, they inhibited the invasion and migration of HCC cells. In an ex vivo model, the extracts significantly inhibited tumor cell growth and induced apoptosis by increasing the expression of the cleaved caspase-3. A mechanistic study revealed that they effectively suppressed PI3K/AKT/mTOR signaling pathways in HCC cells. Taken together, our findings demonstrate that they could efficiently not only induce apoptosis but also inhibit cell growth, migration, and invasion of human HCC cells by blocking the PI3K/AKT/mTOR pathway. We suggest XS-5 and XS-6 as novel natural anti-HCC agents.

Download Full-text