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Metabolomics

, 13:39 | Cite as

Triterpenoid-rich loquat leaf extract induces growth inhibition and apoptosis of pancreatic cancer cells through altering key flux ratios of glucose metabolism

  • Qing-Yi Lu
  • Xuemei Zhang
  • Jieping Yang
  • Vay-Liang W. Go
  • Wai-Nang Lee
Original Article

Abstract

Introduction

Loquat leaf extract (LLE) is a mixture rich in terpenoids, and has broad biological activities including the inhibition of cancer cell growth. The exact metabolic mechanism of this growth inhibiting effect is not known.

Objectives

We investigated the cellular metabolic effect of LLE, and ursolic acid (UA) on pancreatic cancer cells using a 13C carbon tracing technology.

Methods

MIA PaCa-2 cells were cultured in medium containing [1, 2 13C2]-glucose in the presence of either LLE (50 µg/ml), UA (50 µM), or metformin (1 mM). The mass isotopomer distribution of glucose, lactate, ribose, glutamate and palmitate in medium was determined. Based on the mass isotopomer distribution in metabolites we were able to determine individual 13C enrichment (∑M × n) and the minimum fraction of new synthesis (1-M0) in each metabolite. Several flux ratios of energy metabolic pathways were calculated from the mass isotopomer ratios of these metabolites.

Results

We found that tumor viability was suppressed by LLE and UA in a dose dependent manner, and the tumor-inhibiting effect was associated with the changes in oxidative/non-oxidative pentose (Ox/Non-ox) and pyruvate dehydrogenase/isocitrate dehydrogenase (PDH/ICDH) flux ratios resulting in decreased new syntheses of ribose and fatty acids.

Conclusion

Metabolic homeostasis (balance of fluxes) in cancer cells is maintained through the regulation of metabolic fluxes by oncogenes and tumor-suppressor genes. Treatment of MIA PaCa-2 cells by LLE, UA and metformin likely altered key metabolic flux ratios affecting metabolic homeostasis required for energy and macromolecular production in tumor growth.

Keywords

Loquat Triterpenoid MIA PaCa-2 cells Tracer-based metabolomics Mass isotopomer profile 

Abbreviations

UA

Ursolic acid

LLE

Loquat leaf extract

MET

Metformin

Notes

Acknowledgements

This work was supported by the Hirshberg Foundation for Pancreatic Cancer Research and by the National Institutes of Health (P01AT003960).

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest to disclose.

Informed consent

Not applicable.

Research involving human and animals rights

This research did not involve human or animal subjects.

Supplementary material

11306_2017_1176_MOESM1_ESM.doc (46 kb)
Supplementary material 1 (DOC 46 KB)

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Department of MedicineUniversity of CaliforniaLos AngelesUSA
  2. 2.Department of Pediatrics, Harbor-UCLALos Angeles Biomedical Research InstituteTorranceUSA
  3. 3.Department of BiochemistryMedical College of Dalian UniversityDalianChina

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