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.