Antiproliferative and antimetastatic activity of DM-1, sodium 4-[5-(4-hydroxy-3-methoxyphenyl)-3-oxo-penta-1,4-dienyl]-2-methoxy-phenolate, in B16F10 melanoma

ABSTRACT

Melanoma causes 75% of skin cancer deaths mainly due to its high potential to progress to metastasis and by its recognized resistance to conventional therapies. Compound DM-1, sodium 4-[5-(4-hydroxy-3-methoxyphenyl)-3-oxo-penta-1,4-dienyl]-2-methoxy-phenolate, presents structural and biological similarity to curcumin, exhibiting properties such as potent antitumoral and antioxidant activities. In this work, the antitumoral and antiproliferative effects of this compound in in vitro assays with tumor and normal cell lines have been evaluated. Also evaluated was the in vivo antitumoral potential against B16F10 melanoma-bearing mice. Normal and tumor cells were treated with different concentrations of compound DM-1 and the cellular viability was determined by MTT colorimeter assay. The half maximal inhibitory concentration (IC50) found was 30 ìg/mL in B16F10 melanoma cells, while no toxic activity was verified against normal human fibroblastic cells. When DM-1 was administrated by intraperitoneal and endovenous routes to melanoma-bearing animals the survival rate increased by 40% when compared to the control group. Tumor load was reduced by 84% when administered via endovenous and by 54% via intraperitoneal. In conclusion, compound DM-1 acts as selective antitumoral agent inducing cytotoxicity in B16F10 melanoma cells, reducing the tumor load in the treated animals, as well as increasing the survival rate of the animal bearing this neoplasia.