Altered Magnesium Environments Restrict Colorectal HT-29 Spheroid Growth by Disturbing Cellular Mg2+ Homeostasis

Kampuang, Nattida; Lapchock, Pongsakorn; Treerattanakulporn, Tanida; Kongkaew, Phossawee; Chamniansawat, Siriporn; Thongon, Narongrit

doi:10.3390/ijms27020834

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Altered Magnesium Environments Restrict Colorectal HT-29 Spheroid Growth by Disturbing Cellular Mg²⁺ Homeostasis

by

Nattida Kampuang

,

Pongsakorn Lapchock

,

Tanida Treerattanakulporn

,

Phossawee Kongkaew

,

Siriporn Chamniansawat

and

Narongrit Thongon

^*

Department of Medical Sciences, Faculty of Allied Health Sciences, Burapha University, Chonburi 20131, Thailand

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2026, 27(2), 834; https://doi.org/10.3390/ijms27020834

Submission received: 12 December 2025 / Revised: 11 January 2026 / Accepted: 12 January 2026 / Published: 14 January 2026

(This article belongs to the Special Issue The Role of Mg Homeostasis in Disease: 2nd Edition)

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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, Serine 1252, Threonine 1851) and elevated oxidation (e.g., Methionine 1755), suppressed channel activity. High Mg²⁺ caused profound metabolic failure despite increased total Mg²⁺, reflecting functional Mg²⁺ deficiency. CRC spheroids are acutely susceptible to Mg²⁺ imbalance due to collapsed transporter homeostasis and post-translational inhibition of Mg²⁺ channels. These findings reveal a targetable metabolic vulnerability and support the therapeutic potential of localized Mg²⁺ modulation in CRC.

Keywords: colorectal tumor spheroids; magnesium imbalance; low extracellular Mg²⁺ environment; high extracellular Mg²⁺ environment; Mg²⁺ transport mechanisms; TRPM6/7 channel regulation; tumor microenvironment

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MDPI and ACS Style

Kampuang, N.; Lapchock, P.; Treerattanakulporn, T.; Kongkaew, P.; Chamniansawat, S.; Thongon, N. Altered Magnesium Environments Restrict Colorectal HT-29 Spheroid Growth by Disturbing Cellular Mg²⁺ Homeostasis. Int. J. Mol. Sci. 2026, 27, 834. https://doi.org/10.3390/ijms27020834

AMA Style

Kampuang N, Lapchock P, Treerattanakulporn T, Kongkaew P, Chamniansawat S, Thongon N. Altered Magnesium Environments Restrict Colorectal HT-29 Spheroid Growth by Disturbing Cellular Mg²⁺ Homeostasis. International Journal of Molecular Sciences. 2026; 27(2):834. https://doi.org/10.3390/ijms27020834

Chicago/Turabian Style

Kampuang, Nattida, Pongsakorn Lapchock, Tanida Treerattanakulporn, Phossawee Kongkaew, Siriporn Chamniansawat, and Narongrit Thongon. 2026. "Altered Magnesium Environments Restrict Colorectal HT-29 Spheroid Growth by Disturbing Cellular Mg²⁺ Homeostasis" International Journal of Molecular Sciences 27, no. 2: 834. https://doi.org/10.3390/ijms27020834

APA Style

Kampuang, N., Lapchock, P., Treerattanakulporn, T., Kongkaew, P., Chamniansawat, S., & Thongon, N. (2026). Altered Magnesium Environments Restrict Colorectal HT-29 Spheroid Growth by Disturbing Cellular Mg²⁺ Homeostasis. International Journal of Molecular Sciences, 27(2), 834. https://doi.org/10.3390/ijms27020834

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Altered Magnesium Environments Restrict Colorectal HT-29 Spheroid Growth by Disturbing Cellular Mg²⁺ Homeostasis

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