Related Experiment Video

Updated: Jun 20, 2026

Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
07:29

Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment

Published on: April 22, 2019

Heteronemin suppresses chemoresistant oral squamous cell carcinoma cells through ROS-mediated apoptosis and

Chiung-Wei Huang1,2, Fan-Li Lin2,3,4, Chun-Feng Chang5,6

  • 1Department of Physiology, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan.

Apoptosis : an International Journal on Programmed Cell Death
|June 18, 2026
PubMed

Insights

Heteronemin (HET), a marine compound, effectively combats chemoresistant oral squamous cell carcinoma (OSCC) by inducing apoptosis and mitochondrial stress. This compound shows promise as a therapeutic candidate for difficult-to-treat OSCC.

Area of Science:

  • Marine natural products chemistry
  • Cancer biology
  • Molecular pharmacology

Background:

  • Chemoresistance is a significant challenge in treating oral squamous cell carcinoma (OSCC).
  • Novel therapeutic agents are needed to overcome resistance in OSCC.
  • Marine-derived compounds offer a promising source for new cancer therapies.

Purpose of the Study:

  • To investigate the efficacy of heteronemin (HET), a marine sesterterpenoid, against chemoresistant OSCC (SAS-CR) cells.
  • To elucidate the underlying molecular mechanisms of HET's anti-cancer activity.
  • To evaluate HET's therapeutic potential for refractory OSCC.

Main Methods:

  • Cell viability, clonogenic growth, and cytotoxicity assays were performed on SAS-CR cells.
  • Cell cycle analysis and apoptosis markers (caspase-3, PARP, Bax, Bcl-2) were assessed.
  • Transcriptomic profiling, intracellular copper levels, ROS production, and zebrafish xenograft models were utilized.

Main Results:

  • HET demonstrated potent dose- and time-dependent cytotoxicity against SAS-CR cells, surpassing cisplatin and 5-fluorouracil.
  • HET induced S-phase arrest, intrinsic apoptosis via mitochondrial pathways, and metabolic stress, including altered copper homeostasis.
  • HET elevated intracellular copper, increased ROS production, and reduced tumor burden in a zebrafish model with minimal toxicity.

Conclusions:

  • Heteronemin effectively suppresses chemoresistant oral squamous cell carcinoma.
  • HET exerts its effects through ROS-dependent apoptosis and cuproptosis-associated mitochondrial stress.
  • HET represents a promising therapeutic candidate for refractory OSCC.
Keywords:
ApoptosisCuproptosisDrug resistanceHeteroneminOral cancerROS

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