Steviol Represses Glucose Metabolism and Translation Initiation in Pancreatic Cancer Cells

Authors

Sonam Kumari
Mohammed Sikander, The University of Texas Rio Grande Valley
Shabnam Malik, The University of Texas Rio Grande Valley
Manish Tripathi, The University of Texas Rio Grande Valley
Bilal B. Hafeez, The University of Texas Rio Grande ValleyFollow
Murali M. Yallapu, The University of Texas Rio Grande ValleyFollow
Subhash C. Chauhan, The University of Texas Rio Grande ValleyFollow
Sheema Khan, The University of Texas Rio Grande Valley
Meena Jaggi, The University of Texas Rio Grande Valley

Document Type

Article

Publication Date

12-2-2021

Abstract

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.

Comments

© 2021 by the authors.

Recommended Citation

Kumari, S.; Sikander, M.; Malik, S.; Tripathi, M.K.; Hafeez, B.B.; Yallapu, M.M.; Chauhan, S.C.; Khan, S.; Jaggi, M. Steviol Represses Glucose Metabolism and Translation Initiation in Pancreatic Cancer Cells. Biomedicines 2021, 9, 1814. https:// doi.org/10.3390/biomedicines9121814

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Publication Title

Biomedicines

DOI

10.3390/biomedicines9121814

Academic Level

faculty

Mentor/PI Department

Immunology and Microbiology