Enhanced anti-tumor activity of a new curcumin-related compound against melanoma and neuroblastoma cells.
BACKGROUND
Sharing the common neuroectodermal origin, melanoma and neuroblastoma are tumors widely diffused among adult and children, respectively. Clinical prognosis of aggressive neuroectodermal cancers remains dismal, therefore the search for novel therapies against such tumors is warranted. Curcumin is a phytochemical compound widely studied for its antioxidant, anti-inflammatory and anti-cancer properties. Recently, we have synthesized and tested in vitro various curcumin-related compounds in order to select new anti-tumor agents displaying stronger and selective growth inhibition activity on neuroectodermal tumors.


RESULTS
In this work, we have demonstrated that the new alpha,beta-unsaturated ketone D6 was more effective in inhibiting tumor cells growth when compared to curcumin. Normal fibroblasts proliferation was not affected by this treatment. Clonogenic assay showed a significant dose-dependent reduction in both melanoma and neuroblastoma colony formation only after D6 treatment. TUNEL assay, Annexin-V staining, caspases activation and PARP cleavage unveiled the ability of D6 to cause tumor cell death by triggering apoptosis, similarly to curcumin, but with a stronger and quicker extent. These apoptotic features appear to be associated with loss of mitochondrial membrane potential and cytochrome c release. In vivo anti-tumor activity of curcumin and D6 was surveyed using sub-cutaneous melanoma and orthotopic neuroblastoma xenograft models. D6 treated mice exhibited significantly reduced tumor growth compared to both control and curcumin treated ones (Melanoma: D6 vs control: P < 0.001 and D6 vs curcumin P < 0.01; Neuroblastoma: D6 vs both control and curcumin: P < 0.001).


CONCLUSIONS
Our data indicate D6 as a good candidate to develop new therapies against neural crest-derived tumors.
Pisano
Marina
M
Istituto di Chimica Biomolecolare, CNR, Sassari, Italy.
Pagnan
Gabriella
G
Dettori
Maria Antonietta
MA
Cossu
Sara
S
Caffa
Irene
I
Sassu
Ilaria
I
Emionite
Laura
L
Fabbri
Davide
D
Cilli
Michele
M
Pastorino
Fabio
F
Palmieri
Giuseppe
G
Delogu
Giovanna
G
Ponzoni
Mirco
M
Rozzo
Carla
C
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D008545:Melanoma / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009447:Neuroblastoma / Q000473:pathology*; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; D003474:Curcumin