Science et thérapie du cancer

Psammaplin A: A Putative Adjuvant for DNA Damaging Therapies

Abstract

Jamile Charkie

Psammaplin A is a phenolic marine metabolite that exhibits antitumor properties. There is evidence that Psammaplin A is a DNA methyltransferase (DNMT) inhibitor that sensitizes human cancer cells by suppressing DNA repair activity. There is also evidence that the drug is a histone deacetylase. The aim of this experiment is to test the efficacy of Psammaplin A as an anticancer therapeutic agent by comparing its effect on lung cancer cells NCI-H226 Bap1 null cells and on human neuroblastomal SKN cells. In the experiment SKN cells are used because they are more sensitive than normal cells, and toxicity can be discerned better with the use of SKN cells. Results show that at a concentration between 1/10 000 μL and 1/1000 μL of Psammaplin A significantly inhibits cell growth of the Bap1 null cells while presenting minimal toxicity to SKN cells. The results were particularly strong when CPT (a DNA-damage inducing drug) was added to the cells. This indicates that Psammaplin A is a potential adjuvant for cancer patients, particularly for Bap-1 null lung cancer patients being treated with DNA-damage inducing therapies. Results also confirm that Psammaplin A does not affect neuroblastoma or neuroblastomal pathways. Results also indicate, since Psammaplin A inhibition differs from MG132 inhibition of cell proliferation, that Psammaplin A does not inhibit proteasomes.