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Tumor Biology

, Volume 34, Issue 2, pp 1119–1129 | Cite as

The curcumin analog DM-1 induces apoptotic cell death in melanoma

  • Fernanda Faião-Flores
  • José Agustín Quincoces Suarez
  • Silvya Stuchi Maria-Engler
  • Vanessa Soto-Cerrato
  • Ricardo Pérez-Tomás
  • Durvanei Augusto Maria
Research Article

Abstract

The main difficulty in the successful treatment of metastatic melanoma is that this type of cancer is known to be resistant to chemotherapy. Chemotherapy remains the treatment of choice, and dacarbazine (DTIC) is the best standard treatment. The DM-1 compound is a curcumin analog that possesses several curcumin characteristics, such as antiproliferative, antitumor, and antimetastatic properties. The objective of this study was to evaluate the signaling pathways involved in melanoma cell death after treatment with DM-1 compared to the standard agent for melanoma treatment, DTIC. Cell death was evaluated by flow cytometry for annexin V and iodide propide, cleaved caspase 8, and TNF-R1 expression. Hoechst 33342 staining was evaluated by fluorescent microscopy; lipid peroxidation and cell viability (MTT) were evaluated by colorimetric assays. The antiproliferative effects of the drugs were evaluated by flow cytometry for cyclin D1 and Ki67 expression. Mice bearing B16F10 melanoma were treated with DTIC, DM-1, or both therapies. DM-1 induced significant apoptosis as indicated by the presence of cleaved caspase 8 and an increase in TNF-R1 expression in melanoma cells. Furthermore, DM-1 had antiproliferative effects in this the same cell line. DTIC caused cell death primarily by necrosis, and a smaller melanoma cell population underwent apoptosis. DTIC induced oxidative stress and several physiological changes in normal melanocytes, whereas DM-1 did not significantly affect the normal cells. DM-1 antitumor therapy in vivo showed tumor burden decrease with DM-1 monotherapy or in combination with DTIC, besides survival rate increase. Altogether, these data confirm DM-1 as a chemotherapeutic agent with effective tumor control properties and a lower incidence of side effects in normal cells compared to DTIC.

Keywords

Melanoma Dacarbazine (DTIC) DM-1 Curcumin analog Apoptosis Synergism 

Notes

Acknowledgments

The authors are grateful to Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP 2008/56397-8, 2008/58817-4, and 2011/50435-8), the Spanish government, and the European Union (FIS-PI10/00338) for their financial support.

Conflicts of interest

None.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Fernanda Faião-Flores
    • 1
    • 2
  • José Agustín Quincoces Suarez
    • 3
  • Silvya Stuchi Maria-Engler
    • 4
  • Vanessa Soto-Cerrato
    • 5
  • Ricardo Pérez-Tomás
    • 5
  • Durvanei Augusto Maria
    • 1
  1. 1.Laboratory of Biochemistry and BiophysicsButantan InstituteSão PauloBrazil
  2. 2.Faculty of MedicineUniversity of São PauloSão PauloBrazil
  3. 3.Laboratory of Organic SynthesisBandeirante University of São PauloSão PauloBrazil
  4. 4.Department of Clinical Chemistry & Toxicology, School of Pharmaceutical SciencesUniversity of São PauloSão PauloBrazil
  5. 5.Department of Pathology and Experimental Therapeutics, Cancer Cell Biology Research GroupUniversitat de BarcelonaBarcelonaSpain

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