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.
K.V. Balana, J. Princea, Z. Hana, K. Dimasb, M. Cladarasc, J.H. Wychea, N.M. Sitarasd and P. Pantazisa, b, ,
a Department of Biology, University of Miami, Coral Gables, Miami, FL, USA
b Laboratory of Pharmacology–Pharmacotechnology, Foundation for Biomedical Research, Academy of Athens, Greece
c School of Biology, Aristotle University of Thessaloniki, Greece
d Department of Pharmacology, Medical School, University of Athens, Greece
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 G1, 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.
Keywords: Chios mastic gum; Colon cancer cells; Apoptosis; Pistacia lentiscus L. var. chia