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Steviol Represses Glucose Metabolism and Translation Initiation in Pancreatic Cancer Cells
Pancreatic cancer has the worst prognosis and lowest survival rate among all cancers. Pancreatic cancer cells are highly metabolically active and typically reprogrammed for aberrant glucose metabolism; thus they respond poorly to therapeutic modalities. It is highly imperative to understand mechanis...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8698284/ https://www.ncbi.nlm.nih.gov/pubmed/34944630 http://dx.doi.org/10.3390/biomedicines9121814 |
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author | Kumari, Sonam Sikander, Mohammed Malik, Shabnam Tripathi, Manish K. Hafeez, Bilal B. Yallapu, Murali M. Chauhan, Subhash C. Khan, Sheema Jaggi, Meena |
author_facet | Kumari, Sonam Sikander, Mohammed Malik, Shabnam Tripathi, Manish K. Hafeez, Bilal B. Yallapu, Murali M. Chauhan, Subhash C. Khan, Sheema Jaggi, Meena |
author_sort | Kumari, Sonam |
collection | PubMed |
description | Pancreatic cancer has the worst prognosis and lowest survival rate among all cancers. Pancreatic cancer cells are highly metabolically active and typically reprogrammed for aberrant glucose metabolism; thus they respond poorly to therapeutic modalities. It is highly imperative to understand mechanisms that are responsible for high glucose metabolism and identify natural/synthetic agents that can repress glucose metabolic machinery in pancreatic cancer cells, to improve the therapeutic outcomes/management of pancreatic cancer patients. We have identified a glycoside, steviol that effectively represses glucose consumption in pancreatic cancer cells via the inhibition of the translation initiation machinery of the molecular components. Herein, we report that steviol effectively inhibits the glucose uptake and lactate production in pancreatic cancer cells (AsPC1 and HPAF-II). The growth, colonization, and invasion characteristics of pancreatic cancer cells were also determined by in vitro functional assay. Steviol treatment also inhibited the tumorigenic and metastatic potential of human pancreatic cancer cells by inducing apoptosis and cell cycle arrest in the G1/M phase. The metabolic shift by steviol was mediated through the repression of the phosphorylation of mTOR and translation initiation proteins (4E-BP1, eIF4e, eIF4B, and eIF4G). Overall, the results of this study suggest that steviol can effectively suppress the glucose metabolism and translation initiation in pancreatic cancer cells to mitigate their aggressiveness. This study might help in the design of newer combination therapeutic strategies for pancreatic cancer treatment. |
format | Online Article Text |
id | pubmed-8698284 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-86982842021-12-24 Steviol Represses Glucose Metabolism and Translation Initiation in Pancreatic Cancer Cells Kumari, Sonam Sikander, Mohammed Malik, Shabnam Tripathi, Manish K. Hafeez, Bilal B. Yallapu, Murali M. Chauhan, Subhash C. Khan, Sheema Jaggi, Meena Biomedicines Article Pancreatic cancer has the worst prognosis and lowest survival rate among all cancers. Pancreatic cancer cells are highly metabolically active and typically reprogrammed for aberrant glucose metabolism; thus they respond poorly to therapeutic modalities. It is highly imperative to understand mechanisms that are responsible for high glucose metabolism and identify natural/synthetic agents that can repress glucose metabolic machinery in pancreatic cancer cells, to improve the therapeutic outcomes/management of pancreatic cancer patients. We have identified a glycoside, steviol that effectively represses glucose consumption in pancreatic cancer cells via the inhibition of the translation initiation machinery of the molecular components. Herein, we report that steviol effectively inhibits the glucose uptake and lactate production in pancreatic cancer cells (AsPC1 and HPAF-II). The growth, colonization, and invasion characteristics of pancreatic cancer cells were also determined by in vitro functional assay. Steviol treatment also inhibited the tumorigenic and metastatic potential of human pancreatic cancer cells by inducing apoptosis and cell cycle arrest in the G1/M phase. The metabolic shift by steviol was mediated through the repression of the phosphorylation of mTOR and translation initiation proteins (4E-BP1, eIF4e, eIF4B, and eIF4G). Overall, the results of this study suggest that steviol can effectively suppress the glucose metabolism and translation initiation in pancreatic cancer cells to mitigate their aggressiveness. This study might help in the design of newer combination therapeutic strategies for pancreatic cancer treatment. MDPI 2021-12-02 /pmc/articles/PMC8698284/ /pubmed/34944630 http://dx.doi.org/10.3390/biomedicines9121814 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kumari, Sonam Sikander, Mohammed Malik, Shabnam Tripathi, Manish K. Hafeez, Bilal B. Yallapu, Murali M. Chauhan, Subhash C. Khan, Sheema Jaggi, Meena Steviol Represses Glucose Metabolism and Translation Initiation in Pancreatic Cancer Cells |
title | Steviol Represses Glucose Metabolism and Translation Initiation in Pancreatic Cancer Cells |
title_full | Steviol Represses Glucose Metabolism and Translation Initiation in Pancreatic Cancer Cells |
title_fullStr | Steviol Represses Glucose Metabolism and Translation Initiation in Pancreatic Cancer Cells |
title_full_unstemmed | Steviol Represses Glucose Metabolism and Translation Initiation in Pancreatic Cancer Cells |
title_short | Steviol Represses Glucose Metabolism and Translation Initiation in Pancreatic Cancer Cells |
title_sort | steviol represses glucose metabolism and translation initiation in pancreatic cancer cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8698284/ https://www.ncbi.nlm.nih.gov/pubmed/34944630 http://dx.doi.org/10.3390/biomedicines9121814 |
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