Beta-Lap halogenated-derivative PFB as a promising NQO1-dependent anticancer chemotherapeutic against melanoma

LAMBERTI MJ; CHIARAMELLO M; IBARRA LE; UALDEGARAY NS; MORALES VASCONSULO AB; FERREIRA S; RUMIE VITTAR NB; RIVAROLA VA

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

The elevated expression of the NQO1 in many human solid tumors along with its ability to activate quinone-based anticancer agents, such as the natural product β-Lapachone (β-Lap), makes it an excellent target for enzyme-directed drug development. NQO1 plays an important role in the initiation stage of melanoma and its correlation with poor patient outcome make it an intriguing target. The most dangerous aspect of melanoma relay on the metastatic ability in later stages. Therefore, new effective and safe therapeutic agents for metastatic melanoma are needed. In this study, metastasis-derived human melanoma cell lines exhibited higher resistance to β-Lap (LD50 SkMel-2 and 1205Lu: not reached) compared to primary-site derived melanoma cells (LD50 SkMel-28: 1.48 µM) (p