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Iron Metabolism as a Potential Mechanism for Inducing TRAIL-Mediated Extrinsic Apoptosis Using Methylsulfonylmethane

Nipin Sp1, Dong Young Kang1, Eun Seong Jo2

  • 1Department of Pathology, Institute of Biomedical Science and Technology, School of Medicine, Konkuk University, Chungju 27478, Korea.

Cells
|November 27, 2021
PubMed

Insights

Methylsulfonylmethane (MSM) targets embryonic cancer stem cells (CSCs) by inhibiting iron metabolism, inducing TRAIL-mediated apoptosis. This natural compound shows promise for neoadjuvant therapy by suppressing CSCs and reducing cancer recurrence.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Embryonic cancer stem cells (CSCs) possess the potential to differentiate into various cancer types, contributing to tumor recurrence.
  • Natural compounds offer a promising avenue for targeting CSCs with reduced adverse effects.
  • Methylsulfonylmethane (MSM), a sulfur-containing compound, exhibits known anticancer properties.

Purpose of the Study:

  • To elucidate the mechanistic anticancer effects of methylsulfonylmethane (MSM) on embryonic cancer stem cells (CSCs).
  • To investigate MSM's impact on CSC markers and associated signaling pathways.
  • To determine the specific apoptotic pathway induced by MSM in cancer cells.

Main Methods:

  • Western blotting and real-time quantitative PCR (qPCR) were employed for molecular signaling analysis.
  • Flow cytometry was utilized to analyze cellular processes.
  • Specific CSC markers, Wnt/β-catenin signaling, and apoptosis pathways were assessed.

Main Results:

  • MSM significantly inhibited the expression of CSC markers and suppressed Wnt/β-catenin signaling.
  • MSM induced TRAIL-mediated extrinsic apoptosis in NCCIT and NTERA-2 cells, bypassing the intrinsic pathway.
  • MSM's inhibition of iron metabolism-dependent reactive oxygen species (ROS) generation was crucial for TRAIL-mediated apoptosis induction.
  • MSM modulated p38/p53/ERK signaling and microRNA expression (upregulating miR-130a, downregulating miR-221/222), leading to TRAIL induction.

Conclusions:

  • MSM effectively targets embryonic cancer stem cells (CSCs) by inhibiting iron metabolism.
  • MSM induces apoptosis through the TRAIL-mediated extrinsic pathway, offering a novel therapeutic strategy.
  • MSM demonstrates potential as a neoadjuvant therapy agent for cancer by targeting CSCs and their iron metabolism.
Keywords:
MSMNCCITNTERA-2TRAILiron metabolismmiR-130a/miR-221/miR-222p38/p53/ERK signaling

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