6,7-dihydroxy-3,4-dihydroisoquinoline: a novel inhibitor of nuclear factor-kappaB and in vitro invasion in murine mammary cancer cells.
BACKGROUND
The inhibition of nuclear factor (NF)-kappaB with nontoxic agents is a promising possible treatment approach that may inhibit tumor cell proliferation, counteract the prosurvival pathways that mediate resistance to cytotoxic therapy, and prevent tumor cell metastasis.


METHODS
An initial structure-activity relationship study of the NF-kappaB inhibitory activity of acetophenone-type compounds using electrophoretic mobility shift assay and Western blot analysis is presented. An in vitro cell invasion assay using DA3 cells, a murine breast cancer cell line, was conducted to model antimetastatic activity.


RESULTS
The carbonyl moiety is found to be the functional group responsible for inhibition of NF-kappaB, and a novel, more effective agent, 6,7-dihydroxy-3,4-dihydroisoquinoline, is postulated and confirmed. The compounds are characterized as active in the inhibition of both the canonical and noncanonical NF-kappaB signaling pathways. Lastly, 6,7-dihydroxy-3,4-dihydroisoquinoline is discovered to inhibit in vitro invasion in DA3 cells.


CONCLUSIONS
6,7-Dihydroxy-3,4-dihydroisoquionoline and its derivatives are presented as potential prototypes for a novel series of nontoxic antimetastatic agents that can be used in conjunction with current cancer therapeutic techniques.
Alvarez
Francisco N
FN
Pine Crest School, Ft. Lauderdale, Fla., USA.
Carlson
Louise M
LM
Lindner
Inna
I
Lee
Kelvin P
KP
D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D007546:Isoquinolines / Q000737:chemistry / Q000494:pharmacology*; D015674:Mammary Neoplasms, Animal / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
C542354:6,7-dihydroxy-3,4-dihydroisoquinoline; D000098:Acetophenones; D000970:Antineoplastic Agents; D007546:Isoquinolines; D016328:NF-kappa B