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

Nattida Kampuang1, Pongsakorn Lapchock1, Tanida Treerattanakulporn1

  • 1Department of Medical Sciences, Faculty of Allied Health Sciences, Burapha University, Chonburi 20131, Thailand.

International Journal of Molecular Sciences
|January 28, 2026
PubMed

Insights

Colorectal cancer (CRC) spheroids are vulnerable to magnesium (Mg2+) imbalance, showing impaired growth and homeostasis. Targeting Mg2+ transport offers a potential therapeutic strategy for CRC.

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Dysregulated magnesium (Mg2+) homeostasis is linked to colorectal cancer (CRC).
  • The role of extracellular Mg2+ in the CRC tumor microenvironment is not fully understood.

Purpose of the Study:

  • To investigate the effects of sustained low and high extracellular Mg2+ on colorectal cancer (CRC) spheroid (SP) growth and Mg2+ homeostasis.
  • To analyze Mg2+ flux, transporter expression, viability, and molecular alterations in response to Mg2+ stress.

Main Methods:

  • Utilized HT-29 CRC spheroids (SPs) cultured in low or high extracellular Mg2+ environments.
  • Assessed Mg2+ flux, expression of Mg2+ transporters (e.g., Transient Receptor Potential Melastatin (TRPM) 6), cell viability, apoptosis, autophagy, and phospho-/oxidoproteomic changes.

Main Results:

  • Both low and high Mg2+ destabilized SP architecture, reduced viability, and induced apoptosis and autophagy.
  • SPs exhibited increased vulnerability compared to 2D cultures, with impaired Mg2+ influx and disrupted transporter regulation.
  • Altered phosphorylation and increased oxidation of TRPM6/7 channels suppressed their activity, leading to functional Mg2+ deficiency even under high Mg2+ conditions.

Conclusions:

  • Colorectal cancer (CRC) spheroids are highly susceptible to Mg2+ imbalance due to compromised transporter homeostasis and inhibited Mg2+ channels.
  • These findings highlight a targetable metabolic vulnerability in CRC.
  • Localized Mg2+ modulation presents a potential therapeutic avenue for CRC treatment.
Keywords:
Mg2+ transport mechanismsTRPM6/7 channel regulationcolorectal tumor spheroidshigh extracellular Mg2+ environmentlow extracellular Mg2+ environmentmagnesium imbalancetumor microenvironment

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