title: Antiproliferative activity and induction of apoptosis in human colon cancer cells treated in vitro with constituents of a product derived from Pistacia lentiscus L. var. chia.
abstract: In this report, we demonstrate that a 50% ethanol extract of the plant-derived product, Chios mastic gum (CMG), contains compounds which inhibit proliferation and induce death of HCT116 human colon cancer cells in vitro. CMG-treatment induces cell arrest at G(1), detachment of the cells from the substrate, activation of pro-caspases-8, -9 and -3, and causes several morphological changes typical of apoptosis in cell organelles. These events, furthermore, are time- and dose-dependent, but p53- and p21-independent. Apoptosis induction by CMG is not inhibited in HCT116 cell clones expressing high levels of the anti-apoptotic protein, Bcl-2, or dominant-negative FADD, thereby indicating that CMG induces cell death via a yet-to-be identified pathway, unrelated to the death receptor- and mitochondrion-dependent pathways. The findings presented here suggest that CMG (a) induces an anoikis form of cell death in HCT116 colon cancer cells that includes events associated with caspase-dependent pathways; and (b) might be developed into a chemotherapeutic agent for the treatment of human colon and other cancers.
authors.affiliation: Department of Biology, University of Miami, Coral Gables, Miami, FL, USA.
authors.forename: K V
authors.initials: KV
authors.lastname: Balan
authors.forename: J
authors.initials: J
authors.lastname: Prince
authors.forename: Z
authors.initials: Z
authors.lastname: Han
authors.forename: K
authors.initials: K
authors.lastname: Dimas
authors.forename: M
authors.initials: M
authors.lastname: Cladaras
authors.forename: J H
authors.initials: JH
authors.lastname: Wyche
authors.forename: N M
authors.initials: NM
authors.lastname: Sitaras
authors.forename: P
authors.initials: P
authors.lastname: Pantazis
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects / Q000648:ultrastructure; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D008517:Phytotherapy; D027927:Pistacia; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts