Effect of Magnesium Supplementation to Prevent Nephrotoxicity on the Antitumor Activity of Cisplatin

Megumi Yasuda; Shuichi Kishimoto; Rika Ebara; Manabu Amano; Shoji Fukushima

doi:doi:10.11648/j.jctr.20190702.13

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Effect of Magnesium Supplementation to Prevent Nephrotoxicity on the Antitumor Activity of Cisplatin

Megumi Yasuda, Shuichi Kishimoto, Rika Ebara, Manabu Amano, Shoji Fukushima

Published in Journal of Cancer Treatment and Research (Volume 7, Issue 2)

Received: 5 August 2019 Accepted: 24 August 2019 Published: 9 September 2019

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Abstract

Background: Cisplatin (CDDP) is one of the most widely used anticancer drugs, but CDDP often leads to nephrotoxicity, which limits its clinical effectiveness. Magnesium (Mg) supplementation is recommended for the avoidance of CDDP-induced nephrotoxicity. However, there is a concern that exposing cancer cells to Mg may suppress the antitumor effect of CDDP. Methods: Transporter expression, intracellular platinum and Mg levels, and cytotoxicity of CDDP after Mg exposure were assessed in human hepatocellular carcinoma (HepG2) and human ovarian carcinoma (2008) cells. Results: In HepG2 cells, Mg exposure significantly increased mRNA levels of multidrug and toxin extrusion 1 (MATE1), which mediates the renal excretion of CDDP, but did not alter its protein levels, including those of organic cation transporter 1 (OCT1), which mediates CDDP uptake in renal tubular and cancer cells, and multidrug resistance-associated protein 2 (MRP2), which mediates CDDP efflux in cancer cells. In 2008 cells, MATE1 protein expression could not be detected, but a slight increase in MRP2 and OCT1 protein expression was observed after Mg exposure. Intracellular Mg levels were significantly increased due to Mg exposure in both cells. However, intracellular platinum levels and cytotoxicity of CDDP were not affected in both cells, even with 2 mM Mg co-exposure. Conclusion: This study found that Mg exposure only slightly changed transporter expression and did not affect intracellular platinum levels and CDDP cytotoxicity in HepG2 and 2008 cells. Thus, Mg supplementation can be used to avoid CDDP-induced renal toxicity without affecting the accumulation of CDDP in cancer cells and its cytotoxicity.

Published in	Journal of Cancer Treatment and Research (Volume 7, Issue 2)
DOI	10.11648/j.jctr.20190702.13
Page(s)	41-46
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2019. Published by Science Publishing Group

Keywords

Cisplatin, Magnesium, Transporter, Accumulation

References

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APA Style

Megumi Yasuda, Shuichi Kishimoto, Rika Ebara, Manabu Amano, Shoji Fukushima. (2019). Effect of Magnesium Supplementation to Prevent Nephrotoxicity on the Antitumor Activity of Cisplatin. Journal of Cancer Treatment and Research, 7(2), 41-46. https://doi.org/10.11648/j.jctr.20190702.13

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ACS Style

Megumi Yasuda; Shuichi Kishimoto; Rika Ebara; Manabu Amano; Shoji Fukushima. Effect of Magnesium Supplementation to Prevent Nephrotoxicity on the Antitumor Activity of Cisplatin. J. Cancer Treat. Res. 2019, 7(2), 41-46. doi: 10.11648/j.jctr.20190702.13

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AMA Style

Megumi Yasuda, Shuichi Kishimoto, Rika Ebara, Manabu Amano, Shoji Fukushima. Effect of Magnesium Supplementation to Prevent Nephrotoxicity on the Antitumor Activity of Cisplatin. J Cancer Treat Res. 2019;7(2):41-46. doi: 10.11648/j.jctr.20190702.13

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@article{10.11648/j.jctr.20190702.13,
  author = {Megumi Yasuda and Shuichi Kishimoto and Rika Ebara and Manabu Amano and Shoji Fukushima},
  title = {Effect of Magnesium Supplementation to Prevent Nephrotoxicity on the Antitumor Activity of Cisplatin},
  journal = {Journal of Cancer Treatment and Research},
  volume = {7},
  number = {2},
  pages = {41-46},
  doi = {10.11648/j.jctr.20190702.13},
  url = {https://doi.org/10.11648/j.jctr.20190702.13},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.jctr.20190702.13},
  abstract = {Background: Cisplatin (CDDP) is one of the most widely used anticancer drugs, but CDDP often leads to nephrotoxicity, which limits its clinical effectiveness. Magnesium (Mg) supplementation is recommended for the avoidance of CDDP-induced nephrotoxicity. However, there is a concern that exposing cancer cells to Mg may suppress the antitumor effect of CDDP. Methods: Transporter expression, intracellular platinum and Mg levels, and cytotoxicity of CDDP after Mg exposure were assessed in human hepatocellular carcinoma (HepG2) and human ovarian carcinoma (2008) cells. Results: In HepG2 cells, Mg exposure significantly increased mRNA levels of multidrug and toxin extrusion 1 (MATE1), which mediates the renal excretion of CDDP, but did not alter its protein levels, including those of organic cation transporter 1 (OCT1), which mediates CDDP uptake in renal tubular and cancer cells, and multidrug resistance-associated protein 2 (MRP2), which mediates CDDP efflux in cancer cells. In 2008 cells, MATE1 protein expression could not be detected, but a slight increase in MRP2 and OCT1 protein expression was observed after Mg exposure. Intracellular Mg levels were significantly increased due to Mg exposure in both cells. However, intracellular platinum levels and cytotoxicity of CDDP were not affected in both cells, even with 2 mM Mg co-exposure. Conclusion: This study found that Mg exposure only slightly changed transporter expression and did not affect intracellular platinum levels and CDDP cytotoxicity in HepG2 and 2008 cells. Thus, Mg supplementation can be used to avoid CDDP-induced renal toxicity without affecting the accumulation of CDDP in cancer cells and its cytotoxicity.},
 year = {2019}
}

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TY  - JOUR
T1  - Effect of Magnesium Supplementation to Prevent Nephrotoxicity on the Antitumor Activity of Cisplatin
AU  - Megumi Yasuda
AU  - Shuichi Kishimoto
AU  - Rika Ebara
AU  - Manabu Amano
AU  - Shoji Fukushima
Y1  - 2019/09/09
PY  - 2019
N1  - https://doi.org/10.11648/j.jctr.20190702.13
DO  - 10.11648/j.jctr.20190702.13
T2  - Journal of Cancer Treatment and Research
JF  - Journal of Cancer Treatment and Research
JO  - Journal of Cancer Treatment and Research
SP  - 41
EP  - 46
PB  - Science Publishing Group
SN  - 2376-7790
UR  - https://doi.org/10.11648/j.jctr.20190702.13
AB  - Background: Cisplatin (CDDP) is one of the most widely used anticancer drugs, but CDDP often leads to nephrotoxicity, which limits its clinical effectiveness. Magnesium (Mg) supplementation is recommended for the avoidance of CDDP-induced nephrotoxicity. However, there is a concern that exposing cancer cells to Mg may suppress the antitumor effect of CDDP. Methods: Transporter expression, intracellular platinum and Mg levels, and cytotoxicity of CDDP after Mg exposure were assessed in human hepatocellular carcinoma (HepG2) and human ovarian carcinoma (2008) cells. Results: In HepG2 cells, Mg exposure significantly increased mRNA levels of multidrug and toxin extrusion 1 (MATE1), which mediates the renal excretion of CDDP, but did not alter its protein levels, including those of organic cation transporter 1 (OCT1), which mediates CDDP uptake in renal tubular and cancer cells, and multidrug resistance-associated protein 2 (MRP2), which mediates CDDP efflux in cancer cells. In 2008 cells, MATE1 protein expression could not be detected, but a slight increase in MRP2 and OCT1 protein expression was observed after Mg exposure. Intracellular Mg levels were significantly increased due to Mg exposure in both cells. However, intracellular platinum levels and cytotoxicity of CDDP were not affected in both cells, even with 2 mM Mg co-exposure. Conclusion: This study found that Mg exposure only slightly changed transporter expression and did not affect intracellular platinum levels and CDDP cytotoxicity in HepG2 and 2008 cells. Thus, Mg supplementation can be used to avoid CDDP-induced renal toxicity without affecting the accumulation of CDDP in cancer cells and its cytotoxicity.
VL  - 7
IS  - 2
ER  -

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Author Information

Megumi Yasuda

Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe, Japan
Shuichi Kishimoto

Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Kobe, Japan
Rika Ebara

Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Kobe, Japan
Manabu Amano

Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe, Japan
Shoji Fukushima

Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Kobe, Japan

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APA Style

Megumi Yasuda, Shuichi Kishimoto, Rika Ebara, Manabu Amano, Shoji Fukushima. (2019). Effect of Magnesium Supplementation to Prevent Nephrotoxicity on the Antitumor Activity of Cisplatin. Journal of Cancer Treatment and Research, 7(2), 41-46. https://doi.org/10.11648/j.jctr.20190702.13

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ACS Style

Megumi Yasuda; Shuichi Kishimoto; Rika Ebara; Manabu Amano; Shoji Fukushima. Effect of Magnesium Supplementation to Prevent Nephrotoxicity on the Antitumor Activity of Cisplatin. J. Cancer Treat. Res. 2019, 7(2), 41-46. doi: 10.11648/j.jctr.20190702.13

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AMA Style

Megumi Yasuda, Shuichi Kishimoto, Rika Ebara, Manabu Amano, Shoji Fukushima. Effect of Magnesium Supplementation to Prevent Nephrotoxicity on the Antitumor Activity of Cisplatin. J Cancer Treat Res. 2019;7(2):41-46. doi: 10.11648/j.jctr.20190702.13

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@article{10.11648/j.jctr.20190702.13,
  author = {Megumi Yasuda and Shuichi Kishimoto and Rika Ebara and Manabu Amano and Shoji Fukushima},
  title = {Effect of Magnesium Supplementation to Prevent Nephrotoxicity on the Antitumor Activity of Cisplatin},
  journal = {Journal of Cancer Treatment and Research},
  volume = {7},
  number = {2},
  pages = {41-46},
  doi = {10.11648/j.jctr.20190702.13},
  url = {https://doi.org/10.11648/j.jctr.20190702.13},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.jctr.20190702.13},
  abstract = {Background: Cisplatin (CDDP) is one of the most widely used anticancer drugs, but CDDP often leads to nephrotoxicity, which limits its clinical effectiveness. Magnesium (Mg) supplementation is recommended for the avoidance of CDDP-induced nephrotoxicity. However, there is a concern that exposing cancer cells to Mg may suppress the antitumor effect of CDDP. Methods: Transporter expression, intracellular platinum and Mg levels, and cytotoxicity of CDDP after Mg exposure were assessed in human hepatocellular carcinoma (HepG2) and human ovarian carcinoma (2008) cells. Results: In HepG2 cells, Mg exposure significantly increased mRNA levels of multidrug and toxin extrusion 1 (MATE1), which mediates the renal excretion of CDDP, but did not alter its protein levels, including those of organic cation transporter 1 (OCT1), which mediates CDDP uptake in renal tubular and cancer cells, and multidrug resistance-associated protein 2 (MRP2), which mediates CDDP efflux in cancer cells. In 2008 cells, MATE1 protein expression could not be detected, but a slight increase in MRP2 and OCT1 protein expression was observed after Mg exposure. Intracellular Mg levels were significantly increased due to Mg exposure in both cells. However, intracellular platinum levels and cytotoxicity of CDDP were not affected in both cells, even with 2 mM Mg co-exposure. Conclusion: This study found that Mg exposure only slightly changed transporter expression and did not affect intracellular platinum levels and CDDP cytotoxicity in HepG2 and 2008 cells. Thus, Mg supplementation can be used to avoid CDDP-induced renal toxicity without affecting the accumulation of CDDP in cancer cells and its cytotoxicity.},
 year = {2019}
}

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TY  - JOUR
T1  - Effect of Magnesium Supplementation to Prevent Nephrotoxicity on the Antitumor Activity of Cisplatin
AU  - Megumi Yasuda
AU  - Shuichi Kishimoto
AU  - Rika Ebara
AU  - Manabu Amano
AU  - Shoji Fukushima
Y1  - 2019/09/09
PY  - 2019
N1  - https://doi.org/10.11648/j.jctr.20190702.13
DO  - 10.11648/j.jctr.20190702.13
T2  - Journal of Cancer Treatment and Research
JF  - Journal of Cancer Treatment and Research
JO  - Journal of Cancer Treatment and Research
SP  - 41
EP  - 46
PB  - Science Publishing Group
SN  - 2376-7790
UR  - https://doi.org/10.11648/j.jctr.20190702.13
AB  - Background: Cisplatin (CDDP) is one of the most widely used anticancer drugs, but CDDP often leads to nephrotoxicity, which limits its clinical effectiveness. Magnesium (Mg) supplementation is recommended for the avoidance of CDDP-induced nephrotoxicity. However, there is a concern that exposing cancer cells to Mg may suppress the antitumor effect of CDDP. Methods: Transporter expression, intracellular platinum and Mg levels, and cytotoxicity of CDDP after Mg exposure were assessed in human hepatocellular carcinoma (HepG2) and human ovarian carcinoma (2008) cells. Results: In HepG2 cells, Mg exposure significantly increased mRNA levels of multidrug and toxin extrusion 1 (MATE1), which mediates the renal excretion of CDDP, but did not alter its protein levels, including those of organic cation transporter 1 (OCT1), which mediates CDDP uptake in renal tubular and cancer cells, and multidrug resistance-associated protein 2 (MRP2), which mediates CDDP efflux in cancer cells. In 2008 cells, MATE1 protein expression could not be detected, but a slight increase in MRP2 and OCT1 protein expression was observed after Mg exposure. Intracellular Mg levels were significantly increased due to Mg exposure in both cells. However, intracellular platinum levels and cytotoxicity of CDDP were not affected in both cells, even with 2 mM Mg co-exposure. Conclusion: This study found that Mg exposure only slightly changed transporter expression and did not affect intracellular platinum levels and CDDP cytotoxicity in HepG2 and 2008 cells. Thus, Mg supplementation can be used to avoid CDDP-induced renal toxicity without affecting the accumulation of CDDP in cancer cells and its cytotoxicity.
VL  - 7
IS  - 2
ER  -

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