Research Papers:

In vitro chemotherapy-associated muscle toxicity is attenuated with nutritional support, while treatment efficacy is retained

Liza A. Wijler, Francina J. Dijk, Hanil Quirindongo, Danielle A.E. Raats, Bram Dorresteijn, Matthew J.W. Furber, Anne M. May, Onno Kranenburg and Miriam van Dijk _

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Oncotarget. 2022; 13:1094-1108. https://doi.org/10.18632/oncotarget.28279

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Liza A. Wijler1,*, Francina J. Dijk2,*, Hanil Quirindongo2, Danielle A.E. Raats1, Bram Dorresteijn2, Matthew J.W. Furber2, Anne M. May3, Onno Kranenburg1,4 and Miriam van Dijk2

1 Laboratory of Translational Oncology, Division of Imaging and Cancer, University Medical Centre Utrecht, 3584 CX, Utrecht, The Netherlands

2 Danone Nutricia Research, 3584 CT, Utrecht, The Netherlands

3 Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, 3584 CG, Utrecht, The Netherlands

4 Utrecht Platform for Organoid Technology, Utrecht University, 3584 CS, Utrecht, The Netherlands

* Shared first author

Correspondence to:

Miriam van Dijk, email: miriam.vandijk@danone.com

Keywords: C2C12 myotubes; chemotherapy; chemotherapy-associated toxicity; colorectal cancer; nutrients; tumor (organoid) cells

Received: April 04, 2022     Accepted: September 09, 2022     Published: October 08, 2022

Copyright: © 2022 Wijler et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Purpose: Muscle-wasting and treatment-related toxicities negatively impact prognosis of colorectal cancer (CRC) patients. Specific nutritional composition might support skeletal muscle and enhance treatment support. In this in vitro study we assess the effect of nutrients EPA, DHA, L-leucine and vitamin D3, as single nutrients or in combination on chemotherapy-treated C2C12-myotubes, and specific CRC-tumor cells.

Materials and Methods: Using C2C12-myotubes, the effects of chemotherapy (oxaliplatin, 5-fluorouracil, oxaliplatin+5-fluorouracil and irinotecan) on protein synthesis, cell-viability, caspase-3/7-activity and LDH-activity were assessed. Addition of EPA, DHA, L-leucine and vitamin D3 and their combination (SNCi) were studied in presence of above chemotherapies. Tumor cell-viability was assessed in oxaliplatin-treated C26 and MC38 CRC cells, and in murine and patient-derived CRC-organoids.

Results: While chemotherapy treatment of C2C12-myotubes decreased protein synthesis, cell-viability and increased caspase-3/7 and LDH-activity, SNCi showed improved protein synthesis and cell viability and lowered LDH activity. The nutrient combination SNCi showed a better overall performance compared to the single nutrients. Treatment response of tumor models was not significantly affected by addition of nutrients.

Conclusions: This in vitro study shows protective effect with specific nutrition composition of C2C12-myotubes against chemotherapy toxicity, which is superior to the single nutrients, while treatment response of tumor cells remained.

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