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. 2019 Mar 16;11(3):376. doi: 10.3390/cancers11030376

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© 2019 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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Multidrug resistance is associated with an increase of intracellular free Mg²⁺. Intracellular free Mg²⁺ could promote multidrug resistance through three main potential mechanisms: ① Mg²⁺ Џbinds to MDR1 leading to drug extrusion; ② Mg²⁺ enters into the mitochondria through Mrs2 channel leading to Bax inhibition and resistance to apoptosis, ③ Mg²⁺ activates the nuclear PPM1D phosphatase which alters p53 stabilization and protects cancer cells against apoptosis. Chemoresistant cancer cells have a lower Mg²⁺ influx and lower amounts of TRPM6 and TRPM7 channels at the plasma membrane.