Inhibitory Effect of Alnustone on Survival and Lung Metastasis of Colorectal Cancer Cells

Nutrients. 2024 Oct 31;16(21):3737. doi: 10.3390/nu16213737.

Abstract

Background/objectives: Alnustone (Aln) is an effective compound of Alpinia katsumadae Hayata. Aln possesses various pharmacological activities such as antibacterial, anti-inflammatory, and anti-cancer effects. However, the inhibitory effect of Aln on colorectal cancer (CRC) has not yet been identified. Thus, research was conducted to clarify whether Aln can suppress the proliferative and metastatic ability of CRC cells.

Methods: A cell viability assay was performed to confirm the decrease in CRC cell viability following Aln treatment. Flow cytometry was carried out to evaluate the effects of Aln on cell cycle arrest, autophagy, and apoptosis in CRC cells. In addition, a lung metastasis animal model was used to check the inhibitory effect of Aln on the metastasis of CRC cells.

Results: Aln remarkably diminished the viability and colony-forming ability of several CRC cell lines. In addition, Aln led to a halt at the G0/G1 phase through downregulating cyclin D1-CDK4 in CRC cells. The upregulation of LC3B and p62 expression by Aln triggered autophagy of CRC cells. Moreover, Aln promoted mitochondrial depolarization, resulting in apoptosis of CRC cells. Oral administration of Aln significantly restrained the metastasized lung tumor nodules.

Conclusions: This study demonstrated that Aln can suppress the survival and lung metastasis of CRC cells by promoting cell cycle arrest, autophagy, and apoptosis.

Keywords: alnustone; apoptosis; autophagy; cell cycle arrest; colorectal cancer; lung metastasis.

MeSH terms

  • Alpinia / chemistry
  • Animals
  • Apoptosis* / drug effects
  • Autophagy* / drug effects
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival* / drug effects
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / pathology
  • Cyclin D1 / metabolism
  • Cyclin-Dependent Kinase 4 / metabolism
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / secondary
  • Male
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Microtubule-Associated Proteins
  • Xenograft Model Antitumor Assays

Substances

  • Cyclin-Dependent Kinase 4
  • Cyclin D1
  • CDK4 protein, human
  • CCND1 protein, human
  • MAP1LC3B protein, human
  • Microtubule-Associated Proteins

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