Nuciferine Inhibits Oral Squamous Cell Carcinoma Partially through Suppressing the STAT3 Signaling Pathway

Int J Mol Sci. 2023 Sep 26;24(19):14532. doi: 10.3390/ijms241914532.

Abstract

Oral squamous cell carcinoma (OSCC) poses a significant obstacle to the worldwide healthcare system. Discovering efficient and non-toxic medications is crucial for managing OSCC. Nuciferine, an alkaloid with an aromatic ring, is present in the leaves of Nelumbo nucifera. It has been proven to play a role in multiple biological processes, including the inhibition of inflammation, regulation of the immune system, formation of osteoclasts, and suppression of tumors. Despite the demonstrated inhibitory effects of nuciferine on different types of cancer, there is still a need for further investigation into the therapeutic effects and potential mechanisms of nuciferine in OSCC. Through a series of in vitro experiments, it was confirmed that nuciferine hindered the growth, movement, and infiltration, while enhancing the programmed cell death of OSCC cells. Furthermore, the administration of nuciferine significantly suppressed the signal transducer and activator of transcription 3 (STAT3) signaling pathway in comparison to other signaling pathways. Moreover, the activation of the STAT3 signaling pathway by colivelin resulted in the reversal of nuciferine-suppressed OSCC behaviors. In vivo, we also showed the anti-OSCC impact of nuciferine using the cell-based xenograft (CDX) model in nude mice. Nonetheless, colivelin diminished the tumor-inhibiting impact of nuciferine, suggesting that nuciferine might partially impede the advancement of OSCC by suppressing the STAT3 signaling pathway. Overall, this research could offer a fresh alternative for the pharmaceutical management of OSCC.

Keywords: cell-derived xenograft; nuciferine; oral squamous cell carcinoma; signal transducer and activator of transcription 3; tumor growth.

MeSH terms

  • Animals
  • Aporphines* / therapeutic use
  • Cell Line, Tumor
  • Cell Proliferation
  • Humans
  • Mice
  • Mice, Nude
  • Mouth Neoplasms* / drug therapy
  • Mouth Neoplasms* / pathology
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction
  • Squamous Cell Carcinoma of Head and Neck* / drug therapy

Substances

  • nuciferine
  • STAT3 protein, human
  • STAT3 Transcription Factor
  • Aporphines