title: Mastic oil from Pistacia lentiscus var. chia inhibits growth and survival of human K562 leukemia cells and attenuates angiogenesis.
abstract: Mastic oil from Pistacia lentiscus var. chia, a natural plant extract traditionally used as a food additive, has been extensively studied for its antimicrobial activity attributed to the combination of its bioactive components. One of them, perillyl alcohol (POH), displays tumor chemopreventive, chemotherapeutic, and antiangiogenic properties. We investigated whether mastic oil would also suppress tumor cell growth and angiogenesis. We observed that mastic oil concentration and time dependently exerted an antiproliferative and proapoptotic effect on K562 human leukemia cells and inhibited the release of vascular endothelial growth factor (VEGF) from K562 and B16 mouse melanoma cells. Moreover, mastic oil caused a concentration-dependent inhibition of endothelial cell (EC) proliferation without affecting cell survival and a significant decrease of microvessel formation both in vitro and in vivo. Investigation of underlying mechanism(s) demonstrated that mastic oil reduced 1) in K562 cells the activation of extracellular signal-regulated kinases 1/2 (Erk1/2) known to control leukemia cell proliferation, survival, and VEGF secretion and 2) in EC the activation of RhoA, an essential regulator of neovessel organization. Overall, our results underscore that mastic oil, through its multiple effects on malignant cells and ECs, may be a useful natural dietary supplement for cancer prevention.
authors.affiliation: G.P. Livanos andM. Simou Laboratories, Evangelismos Hospital, Department of Critical Careand Pulmonary Services, Medical School, University of Athens, 10675 Athens, Greece. elloutrar@med.uoa.gr
authors.forename: Heleni
authors.initials: H
authors.lastname: Loutrari
authors.forename: Sophia
authors.initials: S
authors.lastname: Magkouta
authors.forename: Anastasia
authors.initials: A
authors.lastname: Pyriochou
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Koika
authors.forename: Fragiskos N
authors.initials: FN
authors.lastname: Kolisis
authors.forename: Andreas
authors.initials: A
authors.lastname: Papapetropoulos
authors.forename: Charis
authors.initials: C
authors.lastname: Roussos
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D020014:K562 Cells; D008546:Melanoma, Experimental; D051379:Mice; D039821:Monoterpenes / Q000494:pharmacology*; D027927:Pistacia / Q000737:chemistry*; D010938:Plant Oils / Q000494:pharmacology*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D039821:Monoterpenes; D010938:Plant Oils; D042461:Vascular Endothelial Growth Factor A; C032208:perillyl alcohol