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Contribution of p38 MAPK Pathway to Norcantharidin-Induced Programmed Cell Death in Human Oral Squamous Cell

Chi-Hyun Ahn1, Kyoung-Ok Hong1, Bohwan Jin2

  • 1Department of Oral Pathology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 03080, Korea.

International Journal of Molecular Sciences
|July 19, 2019
PubMed

Insights

Norcantharidin (NCTD) effectively inhibits oral squamous cell carcinoma (OSCC) growth by inducing apoptosis through p38 MAPK pathway activation. This study suggests NCTD as a potential anticancer drug for OSCC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Norcantharidin (NCTD), a cantharidin analog, shows anticancer potential.
  • The precise mechanisms of NCTD against oral squamous cell carcinoma (OSCC) remain unclear.

Purpose of the Study:

  • To investigate the apoptotic effects and molecular targets of NCTD in human OSCC.
  • To evaluate NCTD's efficacy in vitro and in vivo.

Main Methods:

  • Cell viability assays (trypan blue, live/dead), western blotting, DAPI staining, flow cytometry, TUNEL assay, and immunohistochemistry were employed.
  • In vivo studies utilized tumor xenografts in mice.
  • Specific pathway inhibitors and genetic manipulation were used to elucidate molecular mechanisms.

Main Results:

  • NCTD significantly inhibited OSCC cell growth and induced apoptosis, evidenced by caspase cleavage, morphological changes, and increased Annexin V-positive cells.
  • NCTD activated the p38 MAPK pathway and inactivated the STAT3 pathway.
  • In vivo, NCTD suppressed tumor growth and increased apoptosis in tumor tissues without causing significant liver or kidney toxicity.

Conclusions:

  • NCTD induces programmed cell death (apoptosis) in OSCC cells primarily through p38 MAPK activation.
  • NCTD demonstrates significant anticancer activity against OSCC in vitro and in vivo.
  • NCTD represents a promising therapeutic candidate for oral squamous cell carcinoma treatment.
Keywords:
norcantharidinoral squamous cell carcinomap38 MAPKprogrammed cell death

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