Induction of apoptosis in human colon cancer HCT116 cells treated with an extract of the plant product, Chios mastic gum.
A hexane extract of the plant product Chios mastic gum (He-CMG) is demonstrated to kill human colon cancer cells in vitro via the process of anoikis. Specifically, the sequence of events includes He-CMG-induced GI-arrest of the cells, detachment of the cells from the substrate and subsequent apoptosis. Anoikis is dependent on the concentration and duration of treatment with He-CMG. Presence of the pan-caspase inhibitor, Z-VAD-fmk, did not prevent cell detachment, but it did prevent apoptosis of the detached cells indicating that the process of cell detachment, but not apoptosis, is independent of caspase activation. He-CMG-induced apoptosis is associated with activation of the initiator caspases-8, and -9 and the effector caspase-3. Caspases are activated in cells at a relatively long time after detachment, and caspase-3 activation may require caspase-8 or caspase-9 activation, as determined by using HCT116 isogenic clones impaired in apoptosis mechanisms that involve these two caspases. Finally, electron microscopy observations indicated a time-dependent appearance of morphological features both typical and non-typical of apoptosis in cells treated with He-CMG for various periods of time. Taken together, the results demonstrated that He-CMG induces apoptosis in HCT116 cells and, therefore, further in vivo and in vitro studies of the anticancer activities of this plant product are warranted.
Balan
Kannan V
KV
Department of Biology, University of Miami, Coral Gables, Miami, FL 33146, USA.
Demetzos
Costas
C
Prince
Jeffrey
J
Dimas
Konstantine
K
Cladaras
Margarita
M
Han
Zhiyong
Z
Wyche
James H
JH
Pantazis
Panayotis
P
D023102:Anoikis / Q000187:drug effects; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects / Q000648:ultrastructure; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D000069997:Mastic Resin; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry*; D010946:Plants, Medicinal / Q000737:chemistry*; D012116:Resins, Plant / Q000627:therapeutic use*; D013997:Time Factors
D000069997:Mastic Resin; D010936:Plant Extracts; D012116:Resins, Plant; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases