Dactylone inhibits epidermal growth factor-induced transformation and phenotype expression of human cancer cells and induces G1-S arrest and apoptosis.
The marine natural chamigrane-type sesquiterpenoid, dactylone, is closely related to secondary metabolites of some edible species of red algae. In the present study, the effect of dactylone was tested on the mouse skin epidermal JB6 P+ Cl41 cell line and its stable transfectants as well as on several human tumor cell lines, including lung (H460), colon (HCT-116), and skin melanomas (SK-MEL-5 and SK-MEL-28). This natural product was effective at nontoxic doses as a cancer-preventive agent, which exerted its actions, at least in part, through the inhibition of cyclin D3 and Cdk4 expression and retinoblastoma tumor suppressor protein (Rb) phosphorylation. The inhibition of these cell cycle components was followed by cell cycle arrest at the G1-S transition with subsequent p53-independent apoptosis. Therefore, these data showed that application of dactylone and related compounds may lead to decreased malignant cell transformation and/or decreased tumor cell proliferation.
Fedorov
Sergey N
SN
Hormel Institute, University of Minnesota, Austin, Minnesota 55912, USA.
Shubina
Larisa K
LK
Bode
Ann M
AM
Stonik
Valentin A
VA
Dong
Zigang
Z
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D004815:Epidermal Growth Factor / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000517:prevention & control*; D010641:Phenotype; D016196:S Phase / Q000187:drug effects; D012717:Sesquiterpenes / Q000494:pharmacology*; D014162:Transfection
D000970:Antineoplastic Agents; D012717:Sesquiterpenes; D004815:Epidermal Growth Factor