A Diet Rich in Fish Oil and Leucine Ameliorates Hypercalcemia in Tumour-Induced Cachectic Mice

Rogier L. C. Plas; Mieke Poland; Joyce Faber; Josep Argiles; Miriam van Dijk; Alessandro Laviano; Jocelijn Meijerink; Renger F. Witkamp; Ardy van Helvoort; Klaske van Norren

doi:10.3390/ijms20204978

A Diet Rich in Fish Oil and Leucine Ameliorates Hypercalcemia in Tumour-Induced Cachectic Mice

Rogier L. C. Plas, Mieke Poland, Joyce Faber, Josep Argiles, Miriam van Dijk, Alessandro Laviano, Jocelijn Meijerink, Renger F. Witkamp, Ardy van Helvoort, Klaske van Norren^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background: Dietary supplementation with leucine and fish oil rich in omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) has previously been shown to reduce cachexia-related outcomes in C26 tumour-bearing mice. To further explore associated processes and mechanisms we investigated changes in plasma Ca2+ levels, the involvement of parathyroid hormone related protein (PTHrP), and its possible interactions with cyclooxygenase 2 (COX-2). Methods: CD2F1 mice were subcutaneously inoculated with C26 adenocarcinoma cells or sham treated and divided in: (1) controls, (2) tumour-bearing controls, and (3) tumour-bearing receiving experimental diets. After 20 days, body and organ masses and total plasma Ca2+ levels were determined. Furthermore, effects of DHA, EPA and leucine on production of PTHrP were studied in cultured C26 cells. Results: The combination of leucine and fish oil reduced tumour-associated hypercalcemia. Plasma Ca2+ levels negatively correlated with carcass mass and multiple organ masses. DHA was able to reduce PTHrP production by C26 cells in vitro. Results indicate that this effect occurred independently of COX-2 inhibition. Conclusion: Our results suggest that cancer-related hypercalcemia may be ameliorated by a nutritional intervention rich in leucine and fish oil. The effect of fish oil possibly relates to a DHA-induced reduction of PTHrP excretion by the tumour.

Original language	English
Article number	4978
Number of pages	12
Journal	International journal of molecular sciences
Volume	20
Issue number	20
DOIs	https://doi.org/10.3390/ijms20204978
Publication status	Published - 2 Oct 2019

Keywords

hypercalcemia
PTHrP
cachexia
fish oil
leucine
DOCOSAHEXAENOIC ACID
PROSTAGLANDIN E-2
CANCER
SUPPLEMENTATION
COMBINATION
CALCIUM
BEARING
PTHRP
CELL
INFLAMMATION

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@article{b1641c4a5025410481bc2717424b4d6a,

title = "A Diet Rich in Fish Oil and Leucine Ameliorates Hypercalcemia in Tumour-Induced Cachectic Mice",

abstract = "Background: Dietary supplementation with leucine and fish oil rich in omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) has previously been shown to reduce cachexia-related outcomes in C26 tumour-bearing mice. To further explore associated processes and mechanisms we investigated changes in plasma Ca2+ levels, the involvement of parathyroid hormone related protein (PTHrP), and its possible interactions with cyclooxygenase 2 (COX-2). Methods: CD2F1 mice were subcutaneously inoculated with C26 adenocarcinoma cells or sham treated and divided in: (1) controls, (2) tumour-bearing controls, and (3) tumour-bearing receiving experimental diets. After 20 days, body and organ masses and total plasma Ca2+ levels were determined. Furthermore, effects of DHA, EPA and leucine on production of PTHrP were studied in cultured C26 cells. Results: The combination of leucine and fish oil reduced tumour-associated hypercalcemia. Plasma Ca2+ levels negatively correlated with carcass mass and multiple organ masses. DHA was able to reduce PTHrP production by C26 cells in vitro. Results indicate that this effect occurred independently of COX-2 inhibition. Conclusion: Our results suggest that cancer-related hypercalcemia may be ameliorated by a nutritional intervention rich in leucine and fish oil. The effect of fish oil possibly relates to a DHA-induced reduction of PTHrP excretion by the tumour.",

keywords = "hypercalcemia, PTHrP, cachexia, fish oil, leucine, DOCOSAHEXAENOIC ACID, PROSTAGLANDIN E-2, CANCER, SUPPLEMENTATION, COMBINATION, CALCIUM, BEARING, PTHRP, CELL, INFLAMMATION",

author = "Plas, {Rogier L. C.} and Mieke Poland and Joyce Faber and Josep Argiles and {van Dijk}, Miriam and Alessandro Laviano and Jocelijn Meijerink and Witkamp, {Renger F.} and {van Helvoort}, Ardy and {van Norren}, Klaske",

note = "Funding Information: Funding: The research was funded by both Nutricia Research and the Wageningen University. Funding Information: Acknowledgments: We would like to thank Judith Hulsman, Jvalini Dwarkasing and Merel van Rooijen for performing part of the in vitro experiments and Diane Kegler for the animal activities and the support of the Animal Care Facility (CKP) of the University of Wageningen. Funding Information: The research was funded by both Nutricia Research and the Wageningen University. We would like to thank Judith Hulsman, Jvalini Dwarkasing and Merel van Rooijen for performing part of the in vitro experiments and Diane Kegler for the animal activities and the support of the Animal Care Facility (CKP) of the University of Wageningen. Publisher Copyright: {\textcopyright} 2019 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2019",

month = oct,

day = "2",

doi = "10.3390/ijms20204978",

language = "English",

volume = "20",

journal = "International journal of molecular sciences",

issn = "1422-0067",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "20",

}

TY - JOUR

T1 - A Diet Rich in Fish Oil and Leucine Ameliorates Hypercalcemia in Tumour-Induced Cachectic Mice

AU - Plas, Rogier L. C.

AU - Poland, Mieke

AU - Faber, Joyce

AU - Argiles, Josep

AU - van Dijk, Miriam

AU - Laviano, Alessandro

AU - Meijerink, Jocelijn

AU - Witkamp, Renger F.

AU - van Helvoort, Ardy

AU - van Norren, Klaske

N1 - Funding Information: Funding: The research was funded by both Nutricia Research and the Wageningen University. Funding Information: Acknowledgments: We would like to thank Judith Hulsman, Jvalini Dwarkasing and Merel van Rooijen for performing part of the in vitro experiments and Diane Kegler for the animal activities and the support of the Animal Care Facility (CKP) of the University of Wageningen. Funding Information: The research was funded by both Nutricia Research and the Wageningen University. We would like to thank Judith Hulsman, Jvalini Dwarkasing and Merel van Rooijen for performing part of the in vitro experiments and Diane Kegler for the animal activities and the support of the Animal Care Facility (CKP) of the University of Wageningen. Publisher Copyright: © 2019 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2019/10/2

Y1 - 2019/10/2

N2 - Background: Dietary supplementation with leucine and fish oil rich in omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) has previously been shown to reduce cachexia-related outcomes in C26 tumour-bearing mice. To further explore associated processes and mechanisms we investigated changes in plasma Ca2+ levels, the involvement of parathyroid hormone related protein (PTHrP), and its possible interactions with cyclooxygenase 2 (COX-2). Methods: CD2F1 mice were subcutaneously inoculated with C26 adenocarcinoma cells or sham treated and divided in: (1) controls, (2) tumour-bearing controls, and (3) tumour-bearing receiving experimental diets. After 20 days, body and organ masses and total plasma Ca2+ levels were determined. Furthermore, effects of DHA, EPA and leucine on production of PTHrP were studied in cultured C26 cells. Results: The combination of leucine and fish oil reduced tumour-associated hypercalcemia. Plasma Ca2+ levels negatively correlated with carcass mass and multiple organ masses. DHA was able to reduce PTHrP production by C26 cells in vitro. Results indicate that this effect occurred independently of COX-2 inhibition. Conclusion: Our results suggest that cancer-related hypercalcemia may be ameliorated by a nutritional intervention rich in leucine and fish oil. The effect of fish oil possibly relates to a DHA-induced reduction of PTHrP excretion by the tumour.

AB - Background: Dietary supplementation with leucine and fish oil rich in omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) has previously been shown to reduce cachexia-related outcomes in C26 tumour-bearing mice. To further explore associated processes and mechanisms we investigated changes in plasma Ca2+ levels, the involvement of parathyroid hormone related protein (PTHrP), and its possible interactions with cyclooxygenase 2 (COX-2). Methods: CD2F1 mice were subcutaneously inoculated with C26 adenocarcinoma cells or sham treated and divided in: (1) controls, (2) tumour-bearing controls, and (3) tumour-bearing receiving experimental diets. After 20 days, body and organ masses and total plasma Ca2+ levels were determined. Furthermore, effects of DHA, EPA and leucine on production of PTHrP were studied in cultured C26 cells. Results: The combination of leucine and fish oil reduced tumour-associated hypercalcemia. Plasma Ca2+ levels negatively correlated with carcass mass and multiple organ masses. DHA was able to reduce PTHrP production by C26 cells in vitro. Results indicate that this effect occurred independently of COX-2 inhibition. Conclusion: Our results suggest that cancer-related hypercalcemia may be ameliorated by a nutritional intervention rich in leucine and fish oil. The effect of fish oil possibly relates to a DHA-induced reduction of PTHrP excretion by the tumour.

KW - hypercalcemia

KW - PTHrP

KW - cachexia

KW - fish oil

KW - leucine

KW - DOCOSAHEXAENOIC ACID

KW - PROSTAGLANDIN E-2

KW - CANCER

KW - SUPPLEMENTATION

KW - COMBINATION

KW - CALCIUM

KW - BEARING

KW - PTHRP

KW - CELL

KW - INFLAMMATION

U2 - 10.3390/ijms20204978

DO - 10.3390/ijms20204978

M3 - Article

C2 - 31600911

SN - 1422-0067

VL - 20

JO - International journal of molecular sciences

JF - International journal of molecular sciences

IS - 20

M1 - 4978

ER -