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Terpenoid‐enriched Loquat Leaf Extract Controls the Growth and Survival of Pancreatic Cancer Cell and Acts on Glucose Metabolsim to Alter Pentose Phosphate Pathway
Author(s) -
Lu QingYi,
Yang Jeiping,
Go VayLiang,
Li Zhaoping,
Lee WaiNang
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.688.15
Subject(s) - pentose phosphate pathway , chemistry , terpenoid , ursolic acid , ampk , biochemistry , eriobotrya , apoptosis , metabolism , glycolysis , biology , japonica , botany , enzyme , protein kinase a , chromatography
Background Eriobotrya japonica (Thunb) Lindl. (Rosaceae), or loquat, is a fruit native to China and Japan. Loquat leaves have been used for the treatment of diabetes mellitus, chronic bronchitis, coughs and skin diseases in traditional Chinese Medicine. The biological active constituents of leaf included terpenoids, which have shown to exhibit anti‐hyperglycemia effect and to promote insulin release by stimulating pancreatic beta‐cells in animal models. Aim The present study investigated novel anti‐tumor activities and the alteration of cellular metabolism by a loquat leaf extract (LLE). Method The terpenoid‐enriched extract was prepared by the extraction of dried leaves growing in Southern California with 75% aqueous ethanol. Mia PaCa‐2 pancreatic adenocarcinoma cells were cultured for 48 hours in presence of various concentrations of LLE and its major terpene constituent ursolic acid (UA), and the effect of LLE and UA on the growth and apoptosis of tumor cells was determined. Using 50% [1, 2 13 C 2 ]‐glucose as a single precursor metabolic tracer, extracellular lactate production as well as intracellular de novo fatty acid palmitate synthesis, acetyl‐CoA and ribonucleotide ribose were measured. Results Our results show that LLE and UA dose‐dependently induce growth suppression and apoptosis, and inhibit phosphor‐AMPK expression. LLE (50 mg/mL) reduces the contribution of glucose to the lactate production and inhibits fatty acid, acetyl‐CoA ( P < 0.01) and ribonucleotide ribose ( P < 0.01) syntheses. Mass isotopomer analysis also reveals that the treatment of LLE results in marked decrease in pentose cycle flux through the oxidative relative to the non‐oxidative pathway ( P < 0.01). Similar results were observed by UA (50 mM) and metformin (1 mM) treatment with the exception that metformin increases lactate production ( P < 0.05). Summary Our study demonstrates that LLE alters glycolysis‐pentose phosphate pathway and controls glucose‐utilizing biomolecule syntheses essential to tumor cell growth and survival. Support or Funding Information Supported by the Hirshberg Foundation for Pancreatic Cancer Research