ABSTRACT
A large number of plants used in traditional medicines have been shown to possess antitumor activities. The aims of this study were to evaluate any anticancer effect of the essential oil (EO) extracted from P. tortuosus against B16F10 melanoma cancer cells in vitro as well as in vivo. In vitro, EO was shown to induce apoptosis and to inhibit migration and invasion processes. Further investigation revealed that EO decreased focal adhesion and invadopodia formation which was accompanied by a drastic downregulation of FAK, Src, ERK, p130Cas and paxillin. Moreover, EO treatment decreased the expression level of p190RhoGAP, and Grb2, which impair cell migration and actin assembly. Mice bearing the melanoma cells were used to confirm any in vivo effectiveness of the EO as an anti-tumor promoting agent. In mice dosed with 100 mg EO/kg/d (for 27 days), tumor weight was inhibited by 98% compared to that in mice that did not receive the product. In conclusion, these data suggested to us that an EO of P. tortuosus could evolve to be a potential medicinal resource for use in the treatment of cancers.
Subject(s)
Apiaceae/chemistry , Focal Adhesion Protein-Tyrosine Kinases/antagonists & inhibitors , Melanoma, Experimental/drug therapy , Oils, Volatile/pharmacology , Proto-Oncogene Proteins pp60(c-src)/antagonists & inhibitors , Animals , Apoptosis/drug effects , Blotting, Western , Cell Line, Tumor , Cell Movement/drug effects , Dose-Response Relationship, Drug , Down-Regulation/drug effects , Focal Adhesion Protein-Tyrosine Kinases/metabolism , Focal Adhesions/drug effects , Humans , Melanoma, Experimental/metabolism , Melanoma, Experimental/pathology , Mice, Inbred BALB C , Neoplasm Invasiveness , Phytotherapy , Proto-Oncogene Proteins pp60(c-src)/metabolism , Tumor Burden/drug effectsABSTRACT
Many studies have been performed to assess potential utility of natural products as immunomodulants to enhance antitumor activity in situ. In this study, an essential oil (EO) from the aerial parts of Pituranthos tortuosus was prepared using hydrodistillation, its composition was characterized, and its immunomodulatory potential was assessed. The results indicated that the EO contained sabinene, α-pinene, limonene, and terpinen-4-ol as major constituents. EO was also found to be able to significantly promote lipopolysaccharide (LPS)-stimulated splenocyte proliferation, suggestive of a potential for activation of B cells and enhanced humoral immune responses in hosts given this product. Effects of EO on cell proliferation and apoptosis were also investigated in B16F10 melanoma cells. EO-induced tumor cell growth inhibition was associated with characteristic apoptotic changes in the cells, including nuclear condensation. In conclusion, these data suggested to us that an EO of P. tortuosus could evolve to be a potential medicinal resource for use in the treatment of cancers.
