Protective Effects of Mastic Oil From Pistacia Lentiscus Variation Chia Against Experimental Growth of Lewis Lung Carcinoma

Abstract

Mastic oil from Pistacia lentiscus variation chia, a traditionally used dietary flavoring agent with medicinal properties, has been shown to exert in vitro antitumor activities, but no study has addressed in vivo efficacy and mechanisms of action. Presently, we demonstrated that treatment of immunocompetent mice with mastic oil (45 mg/kg body weight, intraperitoneally, 3 times a wk for ∼3 wk) significantly inhibited tumor growth (56.4% ± 5.7 maximum reduction in tumor volumes) without toxicity. Analysis of tumors by immunohistochemistry and ELISA indicated that this effect is associated with increased apoptosis, reduced neovascularization, and inhibition of chemokine expression. Likewise mastic oil reduced vascular endothelial growth factor and chemokine release by Lewis lung carcinoma (LLC) cells. Furthermore, mastic oil administration decreased small guanosine triphosphatases (GTPases) Ras, RhoA and nuclear factor-κ-B-dependent reporter gene expression in vivo and in vitro, indicating a mechanistic link between mastic oil activities and blocking of relevant signaling and transcription pathways. A dose-response comparison with perillyl alcohol and α-pinene, two of its components, revealed a higher efficacy of mastic oil, pointing to a beneficial collective interaction among its ingredients. Conclusively, our results provide novel in vivo evidence of mastic oil inhibitory effects on tumor growth and set a rational basis for its future application in cancer prevention.

ACKNOWLEDGMENTS

We wish to thank the Chios Gum Mastic Growers Association (Chios, Greece) and Prof. TS Blackwell (Division of Allergy, Pulmonary, and Critical Care medicine, Vanderbilt University School of Medicine) for providing mastic oil and pNGL-LLC cells, respectively. This work was supported by PENED-03 grant 03ED167 jointly funded from the European Union (75%) and the Hellenic General Secretariat of Research and Technology (25%) and by the “Thorax” Foundation (Athens, Greece).