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Studying Pancreatic Cancer Stem Cell Characteristics for Developing New Treatment Strategies
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Steviol Represses Glucose Metabolism and Translation Initiation in Pancreatic Cancer Cells

Sonam Kumari1, Mohammed Sikander1,2,3, Shabnam Malik1,2,3

  • 1Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN 38163, USA.

Biomedicines
|December 24, 2021
PubMed

Insights

Steviol, a natural compound, inhibits glucose metabolism and translation initiation in pancreatic cancer cells. This discovery offers potential for new combination therapies to combat aggressive pancreatic cancer.

Area of Science:

  • Biochemistry
  • Oncology
  • Molecular Biology

Background:

  • Pancreatic cancer exhibits the poorest prognosis and lowest survival rates among all cancers.
  • Pancreatic cancer cells display high metabolic activity, particularly aberrant glucose metabolism, leading to poor therapeutic response.
  • Understanding high glucose metabolism mechanisms is crucial for developing effective pancreatic cancer treatments.

Purpose of the Study:

  • To identify agents that can repress glucose metabolic machinery in pancreatic cancer cells.
  • To investigate the potential of steviol, a glycoside, in inhibiting pancreatic cancer cell metabolism and aggressiveness.
  • To explore steviol's impact on tumorigenic and metastatic potential.

Main Methods:

  • Assessed steviol's effect on glucose uptake and lactate production in pancreatic cancer cell lines (AsPC1 and HPAF-II).
  • Evaluated in vitro functional assays to determine the impact on cell growth, colonization, and invasion.
  • Analyzed steviol's effect on apoptosis, cell cycle arrest (G1/M phase), and key molecular targets including mTOR and translation initiation factors.

Main Results:

  • Steviol significantly inhibited glucose uptake and lactate production in pancreatic cancer cells.
  • Steviol treatment reduced pancreatic cancer cell growth, colonization, invasion, and metastatic potential.
  • Metabolic reprogramming by steviol involved the repression of mTOR and translation initiation proteins (4E-BP1, eIF4e, eIF4B, eIF4G), inducing apoptosis and G1/M cell cycle arrest.

Conclusions:

  • Steviol effectively suppresses glucose metabolism and translation initiation in pancreatic cancer cells, mitigating their aggressiveness.
  • The findings suggest steviol's potential as a therapeutic agent against pancreatic cancer.
  • This study may guide the development of novel combination therapeutic strategies for pancreatic cancer treatment.
Keywords:
glucose metabolismpancreatic cancerstevioltranslation initiation

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