Altered Magnesium Environments Restrict Colorectal HT-29 Spheroid Growth by Disturbing Cellular Mg2+ Homeostasis
Nattida Kampuang, Pongsakorn Lapchock, Tanida Treerattanakulporn, Phossawee Kongkaew, Siriporn Chamniansawat, Narongrit Thongon
TL;DR
Changing magnesium levels disrupts colorectal cancer spheroid growth by affecting magnesium balance and cell survival.
Contribution
The study reveals how altered magnesium environments specifically impact 3D CRC spheroids through disrupted Mg2+ transporter regulation.
Findings
Low and high extracellular Mg2+ levels destabilize spheroid architecture and reduce cell viability.
Mg2+ stress impairs Mg2+ influx and disrupts TRPM6/7 heterodimers through phosphorylation and oxidation.
High Mg2+ causes metabolic failure in spheroids despite increased total Mg2+ levels.
Abstract
Dysregulated magnesium (Mg2+) homeostasis contributes to colorectal cancer (CRC), yet its context-dependent function within the tumor microenvironment remains unresolved. This study aimed to determine how sustained low and high extracellular Mg2+ environments affect CRC spheroid (SP) growth and Mg2+ homeostasis using HT-29 SPs. We analyzed Mg2+ flux, the expression of Mg2+ transporters (e.g., Transient Receptor Potential Melastatin (TRPM) 6), viability, apoptotic and autophagic markers, and phospho-/oxidoproteomic alterations. Both Mg2+ extremes destabilized SP architecture, reduced viability, and induced apoptosis and autophagy, with SPs displaying heightened vulnerability relative to 2D cultures. Mg2+ stress impaired Mg2+ influx and eliminated adaptive transporter regulation in SPs. Loss of membrane TRPM6/7 heterodimers, driven by altered phosphorylation (e.g., TRPM6 Serine 141,…
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Taxonomy
TopicsMagnesium in Health and Disease · Parathyroid Disorders and Treatments · Magnesium Oxide Properties and Applications