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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...

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Autores principales: Kumari, Sonam, Sikander, Mohammed, Malik, Shabnam, Tripathi, Manish K., Hafeez, Bilal B., Yallapu, Murali M., Chauhan, Subhash C., Khan, Sheema, Jaggi, Meena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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.
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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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