Evidences for the involvement of HER on prodigiosin anticancer effects

Prodigiosin (PG) is a well-know tripyrrole red pigment with immunosuppressive and anticancer activities. Previous studies demonstrated that PG recognizes selectively cells with different levels of ErbB2 expression [1]. In the present work, we evaluated PG activity in two different cell lines: SF-268, glioblastoma cells that present a mutation in the extracellular domain of EGFR, and Malme-3M, metastatic melanoma cells, which expresses approximately equivalent levels of HER-2 and HER-3. PG showed cytotoxic effect in a time-dependent manner with IC₅₀ values ranging from 15.7 to 2.7µM after 24 and 72h of incubation to Malme-3M and 31 to 2.7µM to SF-268, respectively. This effect was accentuated with the simultaneous use of erlotinib (25µM). PG also reduced G₀/G₁ phase and induced DNA fragmentation in Malme-3M cells after 48h of treatment. Differenzial morphology staining indicated that PG induces several morphological alterations like apoptosis and necrosis. These results emphasize the involvement of HER kinases in PG anticancer activity. Reference: [1] Arthaud, IDB et al. (2012) Chemistry & biodiversity 9, p.418–427. Financial Support: CNPq, CAPES, PRONEX.