Marrubenol inhibits osteosarcoma cancer cell growth by inducing autophagic cell death and inhibiting cancer cell migration and invasion.

Purpose: The present study aimed at evaluating the anticancer activity of marrubenol against osteosarcoma cells along with evaluating its effects on autophagic cell death, reactive oxygen species (ROS) generation and cell migration and invasion tendency. Methods: In this study the Saos-2 osteosarcoma cell line was used. Cell cytotoxicity effects were evaluated by MTT cell viability assay, while clonogenic assay assessed the effects on cancer cell colony formation. In vitro wound healing assay was used to evaluate the effects on cell migration. To confirm autophagy, we evaluated the expression of several autophagy-associated proteins Western blot assay along with transmission electron microscopy (TEM). Results: The results indicated that the marrubenol exhibited an IC50 value of 45 mu m and exerted its cytotoxic effects in a dose-dependent manner. Moreover, it was observed that the drug inhibited colony formation and induced autophagy dose-dependently. The underlying mechanism for the induction of autophagy was found to be ROS-mediated and significant inhibition of cell migration as well as cell invasion potential of osteosarcoma cells at the IC50 was observed. Conclusions: These results strongly indicate that marrubenol may be considered as a potent drug lead molecule for the treatment and management of osteosarcoma.