Oncotarget | In Vitro Chemotherapy-associated Muscle Toxicity Attenuated With Nutritional Support, While Treatment Efficacy Retained

“Our in vitro study demonstrates the importance of specialized nutritional support and combining multiple nutrients to reach maximum effect to attenuate chemotherapy-associated muscle toxicity of skeletal muscle in cancer patients.”

BUFFALO, NY- October 11, 2022 – A new research paper was published in Oncotarget's Volume 13 on October 8, 2022, entitled, “In vitro chemotherapy-associated muscle toxicity is attenuated with nutritional support, while treatment efficacy is retained.”

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 new in vitro study, researchers 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, from University Medical Centre Utrecht, Danone Nutricia Research and Utrecht University, assessed the effect of nutrients eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), L-leucine, and vitamin D3 as single nutrients or in combination on chemotherapy-treated C2C12-myotubes and specific CRC-tumor cells.

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 lactic acid dehydrogenase (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.

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.

“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.”

DOI: https://doi.org/10.18632/oncotarget.28279

Correspondence to: Miriam van Dijk - miriam.vandijk@danone.com 

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

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