Dynamized Dilution of Ruta Graveolens Disrupts Plasma Membrane Organization and Decreases Migration of Melanoma Cancer Cells

Background: Cell migration is a complex and heterogeneous process performed by all eukaryotic cell types. Defects in this mechanism could be associated with severe pathologies such as cancer. Cutaneous melanoma is a cancer with poor prognosis mainly because of metastatic dissemination and therefore a deregulation of cell migration. In recent years, preclinical publications studied the effect of homeopathic dilutions such as Ruta graveolens in tumoral cell lines and current therapies can benefit from homeopathy as supportive care in oncology. This study aimed to assess the effects of Ruta graveolens 9CH on plasma membrane reorganization and its influence on melanoma cell migration.

Methods: The overall stiffness of the cellular envelope in melanoma B16F10 cells was measured with atomic force microscopy and calculated by the Young’s modulus. Ruta graveolens 9CH impact on the plasma membrane and actin cytoskeleton organization of B16F10 cells was examined respectively through Laurdan two-photon microscopy for phospholipid organization, cholesterol quantification, and immunofluorescence staining. Migration of Ruta graveolens 9CH-treated B16F10 cells was assessed both in vitro in dispersed cells assay and a transwell migration assay, and in vivo with a melanoma metastasis model.

Results: Ruta graveolens 9CH leads to an in vitro inhibition of migration on fibronectin of B16F10 melanoma cells, as well as a decrease of metastatic dissemination in vivo. These effects appear to be due to a disruption of plasma membrane organization, with a change in cell and membrane stiffness, associated with a disorganization of the actin cytoskeleton and a modification of the lipid composition of the plasma membrane.

Conclusion: Together, these results demonstrate bioactivity of a dynamized dilution of Ruta graveolens 9CH in in vitro and in vivo models of cutaneous melanoma and reinforce its potential as a complementary medicine in oncology.

Keywords: Homeopathy, melanoma, Ruta graveolens, migration, plasma membrane

Publication History

Article published online:
30 January 2024