Abstract
Background
The mammalian target of rapamycin inhibition has been shown to prolong progression-free
survival in patients with pancreatic neuroendocrine tumors. The natural compound baicalein
indirectly inhibits the mammalian target of rapamycin, but it is unknown if baicalein
exhibits such effects at physiologically achievable concentrations or exhibits synergy.
Methods
Pancreatic neuroendocrine tumor cell lines were cultured with baicalein, everolimus,
and/or a synthetic 5’ adenosine monophosphate-activated protein kinase activating
agent alone and in combination. Cell viability assays and immunoblotting were performed.
Female severe combined immunodeficient-beige mice were injected with BON-1 cells and
treated with baicalein and COH-SR4 solutions via oral gavage. Tumor volumes were compared
at 30 days.
Results
Immunoblotting revealed that treatment of baicalein induced 5’ adenosine monophosphate-activated
protein kinase activation and the mammalian target of rapamycin inhibition. Treatment
with baicalein alone led to a significant decrease in the ratio of viable cells compared
with controls at 72 hours at concentrations ≥5 μM (P = .021). The addition of COH-SR4 led to significantly greater effect on cell viability
than with baicalein alone (P < .001, P < .001). The combination of baicalein with everolimus resulted in significantly lower
cell viability than with everolimus alone (P = .005, P < .001). Tumor volume in vivo was significantly decreased with the combination of
baicalein and COH-SR4 compared with controls (P = .003).
Conclusion
Baicalein exhibits antiproliferative effects against pancreatic neuroendocrine tumor
cell lines at doses ≥5 μM and demonstrates synergy.
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Article info
Publication history
Published online: October 04, 2022
Accepted:
July 11,
2022
Identification
Copyright
© 2022 Elsevier Inc. All rights reserved.
