High-Content screening pipeline for natural products targeting oncogenic signaling in melanoma

Authors: Dürr, Lara; Hell, Tanja; Dobrzyński, Maciej; Mattei, Alberto; John, Anika; Augsburger, Nathanja; Bradanini, Gloria; Reinhardt, Jakob K.; Rossberg, Florian; Drobnjakovic, Milos; Gupta, Mahabir P.; Hamburger, Matthias; Pertz, Olivier; Garo, Eliane

Description: The incidence of melanoma, the most fatal dermatological cancer, has dramatically increased over the last few decades. Modern targeted therapy with kinase inhibitors induces potent clinical responses, but drug resistance quickly develops. Combination therapy improves treatment outcomes. Therefore, novel inhibitors targeting aberrant proliferative signaling in melanoma via the MAPK/ERK and PI3K/AKT pathways are urgently needed. Biosensors were combined that report on ERK/AKT activity with image-based highcontent screening and HPLC-based activity profiling. An in-house library of 2576 plant extracts was screened on two melanoma cell lines with different oncogenic mutations leading to pathological ERK/AKT activity. Out of 140 plant extract hits, 44 were selected for HPLC activity profiling. Active thymol derivatives and piperamides from Arnica montana and Piper nigrum were identified that inhibited pathological ERK and/or AKT activity. The pipeline used enabled an efficient identification of natural products targeting oncogenic signaling in melanoma.

Topic: R Medicine (General)
RC0254 Neoplasms. Tumors. Oncology (including Cancer)
RS Pharmacy and materia medica