Enhanced anti-tumor activity of a new curcumin-related compound against melanoma and neuroblastoma cells

Marina Pisano, Gabriella Pagnan, Maria A. Dettori, Sara Cossu, Irene Caffa, Ilaria Sassu, Laura Emionite, Davide Fabbri, Michele Cilli, Fabio Pastorino, Giuseppe Palmieri, Giovanna Delogu, Mirco Ponzoni, Carla Rozzo

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

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 α,β-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.

Original languageEnglish
Article number137
JournalMolecular Cancer
Volume9
DOIs
Publication statusPublished - Jun 3 2010

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Curcumin
Neuroblastoma
Melanoma
Neoplasms
Growth
Neuroectodermal Tumors
Mitochondrial Membrane Potential
Annexin A5
In Situ Nick-End Labeling
Phytochemicals
Therapeutics
Caspases
Cytochromes c
Ketones
Heterografts
Cell Death
Anti-Inflammatory Agents
Fibroblasts
Antioxidants
Apoptosis

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Oncology

Cite this

Enhanced anti-tumor activity of a new curcumin-related compound against melanoma and neuroblastoma cells. / Pisano, Marina; Pagnan, Gabriella; Dettori, Maria A.; Cossu, Sara; Caffa, Irene; Sassu, Ilaria; Emionite, Laura; Fabbri, Davide; Cilli, Michele; Pastorino, Fabio; Palmieri, Giuseppe; Delogu, Giovanna; Ponzoni, Mirco; Rozzo, Carla.

In: Molecular Cancer, Vol. 9, 137, 03.06.2010.

Research output: Contribution to journalArticle

Pisano, Marina ; Pagnan, Gabriella ; Dettori, Maria A. ; Cossu, Sara ; Caffa, Irene ; Sassu, Ilaria ; Emionite, Laura ; Fabbri, Davide ; Cilli, Michele ; Pastorino, Fabio ; Palmieri, Giuseppe ; Delogu, Giovanna ; Ponzoni, Mirco ; Rozzo, Carla. / Enhanced anti-tumor activity of a new curcumin-related compound against melanoma and neuroblastoma cells. In: Molecular Cancer. 2010 ; Vol. 9.
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AU - Pisano, Marina

AU - Pagnan, Gabriella

AU - Dettori, Maria A.

AU - Cossu, Sara

AU - Caffa, Irene

AU - Sassu, Ilaria

AU - Emionite, Laura

AU - Fabbri, Davide

AU - Cilli, Michele

AU - Pastorino, Fabio

AU - Palmieri, Giuseppe

AU - Delogu, Giovanna

AU - Ponzoni, Mirco

AU - Rozzo, Carla

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N2 - 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 α,β-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.

AB - 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 α,β-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.

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