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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Curcumin Analog DM-1 in Monotherapy or Combinatory Treatment with Dacarbazine as a Strategy to Inhibit In Vivo Melanoma Progression

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Author(s):
Faiao-Flores, Fernanda [1] ; Quincoces Suarez, Jose Agustin [2] ; Fruet, Andrea Costa [1] ; Maria-Engler, Silvya Stuchi [1] ; Pardi, Paulo Celso [3] ; Maria, Durvanei Augusto [4]
Total Authors: 6
Affiliation:
[1] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin Chem & Toxicol, Sao Paulo - Brazil
[2] Anhanguera Univ Sao Paulo, Organ Synth Lab, UNIAN, Sao Paulo - Brazil
[3] Anhanguera Univ Sao Paulo, Lab Expt Pathol, UNIAN, Sao Paulo - Brazil
[4] Butantan Inst, Biochem & Biophys Lab, Sao Paulo - Brazil
Total Affiliations: 4
Document type: Journal article
Source: PLoS One; v. 10, n. 3 MAR 5 2015.
Web of Science Citations: 13
Abstract

Malignant melanoma is a highly aggressive form of skin cancer with a high mortality rate if not discovered in early stages. Although a limited number of treatment options for melanoma currently exist, patients with a more aggressive form of this cancer frequently decline treatment. DM-1 is a sodium phenolate and curcumin analog with proven anticancer, anti-proliferative and anti-metastatic properties. In this paper, the DM-1 compound showed in vivo antitumor activity alone or in combination with chemotherapeutic DTIC in B16F10 melanoma-bearing mice. Beneficial effects such as melanoma tumor burden reduction with pyknotic nuclei, decreased nuclei/cytoplasmic ratio and nuclear degradation occurred after DM-1 treatment. No toxicological changes were observed in the liver, kidneys, spleen and lungs after DM-1 monotherapy or DTIC combined therapy. DTIC+DM-1 treatment induced the recovery of anemia arising from melanoma and immunomodulation. Both DM-1 treatment alone and in combination with DTIC induced apoptosis with the cleavage of caspase-3, -8 and -9. Furthermore, melanoma tumors treated with DM-1 showed a preferential apoptotic intrinsic pathway by decreasing Bcl-2/Bax ratio. Considering the chemoresistance exhibited by melanoma towards conventional chemotherapy drugs, DM-1 compound in monotherapy or in combination therapy provides a promising improvement in melanoma treatment with a reduction of side effects. (AU)

FAPESP's process: 11/50435-8 - Synthesis of biologically active phenols and derivatives
Grantee:José Agustín Pablo Quincoces Suárez
Support Opportunities: Regular Research Grants