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Hans E. Grossniklaus, Qing Zhang, Hua Yang, Jack Arbiser; Tris (dibenzyldineacetone) Dipalladium Suppresses Primary Ocular Melanoma And Its Hepatic Metastases In A Murine Ocular Melanoma Model. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3395.
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To evaluate the effect of Tris (Dibenzylideneacetone) Dipalladium (Tris DBA), a N-Myristoyltransferase-1 inhibitor that blocks the myristoylation of substrates and decreases c-Met expression, in control of the size of primary ocular melanoma and the number of hepatic micrometastases in a murine model of ocular melanoma
The posterior compartments of the right eyes of C57BL6 mice were inoculated with 5 x 105/2.5µL B16LS9 melanoma cells. There were two experimental groups (n=15) as follows: group 1, intraperitoneal injection of 3 mg Tris DBA in 250 µl coconut oil, starting at the 1st day, once per day until sacrifice; group 2, intraperitoneal injection of an equal volume of coconut oil as control vehicle. The right eyes were enucleated at the 7 th day to examine primary tumor growth, and the mice were sacrificed at the 21th day after inoculation to examine metastases to the liver. The histologic sections of tumor-bearing eyes and livers were obtained. The size of primary tumor burden was evaluated using Image J and the number of hepatic micrometastases were counted.
The average size of primary ocular melanoma in group 1 with the treatment of Tris DBA was 76038.26 ± 6391.33 pixel2, comparing with 624274.65 ± 130847.84 pixel2 in group 2 treated with the control vehicle (p = 0.008). The number of hepatic micrometastases in mice treated with Tris DBA versus control vehicle was 40.38 ± 1.81 and 84.25 ± 5.28 (p = 0.03), respectively.
This study suggests that Tris (Dibenzylideneacetone) Dipalladium (Tris DBA) suppresses both of the size of primary ocular melanoma and the number of hepatic micrometastases, and is well-tolerated in the murine ocular melanoma model. Further evaluation in vitro of Tris DBA and related complexes is warranted.
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