Protective effects of mastic oil from Pistacia lentiscus variation chia against experimental growth of lewis lung carcinoma.
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 approximately 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-kappa-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 alpha-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.
University of Athens, Athens, Greece.
Sophia
S
Magkouta
Georgios T
GT
Stathopoulos
Ioannis
I
Psallidas
Andreas
A
Papapetropoulos
Fragiskos N
FN
Kolisis
Charis
C
Roussos
Heleni
H
Loutrari
D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D000081008:Bicyclic Monoterpenes; D018827:Carcinoma, Lewis Lung / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008519:Medicine, Traditional; D051379:Mice; D008810:Mice, Inbred C57BL; D039821:Monoterpenes / Q000494:pharmacology; D009368:Neoplasm Transplantation; D008517:Phytotherapy; D027927:Pistacia / Q000737:chemistry; D010938:Plant Oils / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D047368:Tumor Burden / Q000187:drug effects
D043925:Angiogenesis Inducing Agents; D000970:Antineoplastic Agents; D000081008:Bicyclic Monoterpenes; D018836:Inflammation Mediators; D039821:Monoterpenes; D010938:Plant Oils; C032208:perillyl alcohol; C005451:alpha-pinene