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Dihydroartemisinin represses oral squamous cell carcinoma progression through downregulating mitochondrial calcium

Shen Zheng1, Ran Wu2, Yunlong Deng2

  • 1Department of Orthodontics and Prosthodontics, North China University of Science and Technology Affiliated Hospital, Tangshan, Hebei, China.

Bioengineered
|December 1, 2021
PubMed

Insights

Mitochondrial calcium uniporter (MCU) drives oral cancer progression. Dihydroartemisinin (DHA) suppresses oral squamous cell carcinoma (OSCC) by inhibiting MCU, reducing cell proliferation and migration.

Area of Science:

  • Oncology
  • Molecular Biology
  • Mitochondrial Biology

Background:

  • Mitochondrial calcium uniporter (MCU) dysregulation is linked to cancer development.
  • The specific role of MCU in oral squamous cell carcinoma (OSCC) and the mechanisms of dihydroartemisinin (DHA) in suppressing OSCC are not well understood.

Purpose of the Study:

  • To investigate the biological function of MCU in OSCC.
  • To explore the regulatory relationship between MCU and DHA in OSCC.

Main Methods:

  • Immunohistochemistry and Western blot to assess protein expression (MCU, MICU1, MICU2, N-cadherin, TGF-β, vimentin) in OSCC and peritumoral tissues.
  • DHA treatment on CAL-27 cells with MCU knockdown (shMCU) or overexpression (pcDNA3.1-MCU).
  • Assays for cell proliferation (clone formation), mitochondrial membrane potential (MMP), migration (wound healing, Transwell).

Main Results:

  • MCU complex members (MCU, MICU1, MICU2) and epithelial-mesenchymal transition (EMT) markers (N-cadherin, vimentin, TGF-β) were upregulated in OSCC.
  • DHA treatment reduced MCU expression in CAL-27 cells; MCU overexpression counteracted DHA's inhibitory effects.
  • MCU knockdown or DHA treatment suppressed OSCC cell proliferation, MMP, and migration, with DHA reversing MCU overexpression effects.

Conclusions:

  • MCU acts as an oncogene in oral squamous cell carcinoma.
  • Dihydroartemisinin (DHA) suppresses OSCC progression by inhibiting MCU expression, thereby reducing cell proliferation and migration.
Keywords:
Oral squamous cell carcinomadihydroartemisininmigrationmitochondrial calcium uniporterproliferation

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