Disintegrins are low molecular weight peptides derived from viper venom. Previous studies have

shown that disintegrins induce apoptosis, inhibit cell migration, and reduce proliferation of

various cancer cell lines. Three recombinant (r) mojastin peptides (Moj-WN, Moj-MP, and Moj-

DM) were tested for their ability to inhibit migration and proliferation of SK-Mel-28 cells. We

hypothesize that r-Moj-DM and r-Moj-MP will inhibit cell migration and proliferation of SK-

Mel-28. All three r-Moj peptides were produced in the E. coli origami 2 strain that allows for the

formation of disulfide bonds. Recombinant peptides were induced and purified. Cell proliferation

inhibition was measured indirectly using a WST-1 assay. At 3µM, all three r-Moj peptides

inhibited cell proliferation of SK-Mel-28. The r-Moj-MP and r-Moj-DM peptides were the

strongest inhibitors, preventing cell proliferation at 69% and 66%, respectively. The r-Moj-WN

inhibited cell proliferation at 28%. Some of the reduction of cell proliferation by the r-Moj-DM

peptide may be due to apoptosis. In a previous study, we determined that r-Moj-DM induced

apoptosis of SK-Mel-28 cells. We tested r-Moj-MP peptide’s ability to induce apoptosis of SK-

Mel-28 cells, using a tunnel assay, in order to determine if apoptosis induction may explain the

reduction of cell proliferation by r-Moj-MP. At 5 µM, the r-Moj-MP peptide failed to induce

apoptosis, demonstrating that the cell proliferation inhibition by this peptide is not due to

apoptosis. At 3µM, r-Moj-WN failed to inhibit SK-Mel-28 cell migration at significant levels as

compared to the untreated controls (p=0.108). At 3µM, r-Moj-MP and r-Moj-DM inhibited

79.67% (+/- 2.88) and 72% (+/- 2.00) cell migration, respectively. There was no significant

difference between the potency of inhibition between r-Moj-MP and r-Moj-DM peptides

(p=0.012). However, the cell migration inhibition between these peptides and the r-Moj-WN

was significant (p=0.002). Our future studies include the treatment of other cancer cell lines with

the r-Moj-DM and r-Moj-MP peptides in order to determine their effects on cell-migration.

These results will enable us to unravel the signal transduction pathway(s) and the cellular

response(s) that r-Moj-DM and r-Moj-MP may trigger. Funding for this project was provided by

NSF-REU #DBI 1004350, NIH/SCORE # 2SO6 GM008192, and NIH Grant # R25GM071381.