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In vitro treatment of carcinoma cell lines with pancreatic (pro)enzymes suppresses the EMT programme and promotes cell differentiation

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Abstract

Background

Previous research has suggested a putative utility of pancreatic (pro)enzymes in cancer treatment. The aim of the present study was to investigate the in vitro effects of a mixture of two pancreatic pro-enzymes, i.e., Chymotrypsinogen and Trypsinogen, and the enzyme Amylase on three human cancer cell lines, i.e., OE33 (derived from an oesophageal carcinoma), Panc1 (derived from a pancreatic carcinoma) and Caco-2 (derived from a colon carcinoma).

Results

After treatment of the three cancer cell lines with different doses of the (pro)enzymes for up to 7 days, we observed (i) growth inhibition in a dose-dependent manner, (ii) enhanced expression of β-catenin and E-cadherin and decreased expression of several epithelial-mesenchymal transition (EMT)-associated genes, such as Vimentin, Snail and Slug, (iii) differentiation of Caco-2 cells, including the appearance of cell-specific differentiated structures such as microvilli and tight junctions, the acquisition of a more regular polygonal morphology, and an increased expression of the intestinal differentiation markers alkaline phosphatase and cytokeratin 8, and (iv) differentiation of Panc1 cells, including the formation of cell aggregates, an increment on lamellar bodies and an increased expression of the pancreatic differentiation markers glucagon and insulin.

Conclusions

Our results show that the treatment of three different human cancer cell lines with pancreatic (pro)enzymes results in an enhancement of cell adhesion, an attenuation of several EMT-associated markers, and an increase in the expression of several differentiation-associated markers, suggesting the acquisition of a less malignant phenotype and a decrease in proliferative capacity due to lineage-specific cellular differentiation.

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Acknowledgments

Macarena Peran was supported by a grant from Jaen University, Spain (“Plan de Apoyo a la Investigación, Desarrollo Tecnológico e Innovación. IV. Programa de Ayudas a los Investigadores”). Work in the laboratory of Bath University was funded by Propanc Pty Ltd. Work in the laboratory of J.A. Marchal at Granada University was funded by the Instituto de Salud Carlos III (Fondo de Investigación Sanitaria, FEDER, grant number PI10/02295).

Conflict of interest

Dr Julian Kenyon is the Founder and Scientific Director of Propanc Pty Ltd and owns stock in the company. Propanc Pty Ltd and the University of Bath have filed a joint patent from the scientific research undertaken in this report

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Authors and Affiliations

  1. Centre for Regenerative Medicine, Department of Biology & Biochemistry, University of Bath, Bath, UK

    Macarena Perán & David Tosh

  2. Department of Health Sciences, University of Jaén, Paraje de las Lagunillas sn, B3-212, Jaén, 23071, Spain

    Macarena Perán

  3. Department of Human Anatomy and Embryology, University of Granada, Granada, Spain

    Juan Antonio Marchal

  4. Biopathology and Regenerative Medicine Institute (IBIMER), University of Granada, Granada, Spain

    Juan Antonio Marchal

  5. Research Unit, Hospital Universitario Virgen de las Nieves, Granada, Spain

    Maria A. García

  6. The Dove Clinic for Integrated Medicine, The Old Brewery, High Street, Twyford, SO21 1RG, UK

    Julian Kenyon

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  1. Macarena Perán
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  2. Juan Antonio Marchal
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  3. Maria A. García
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Correspondence to Macarena Perán or Julian Kenyon.

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Perán, M., Marchal, J.A., García, M.A. et al. In vitro treatment of carcinoma cell lines with pancreatic (pro)enzymes suppresses the EMT programme and promotes cell differentiation. Cell Oncol. 36, 289–301 (2013). https://doi.org/10.1007/s13402-013-0134-8

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