4.7 Article

High-Content Screening Pipeline for Natural Products Targeting Oncogenic Signaling in Melanoma

Journal

JOURNAL OF NATURAL PRODUCTS
Volume 85, Issue 4, Pages 1006-1017

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acs.jnatprod.1c01154

Keywords

-

Funding

  1. Swiss National Science Foundation [205321-176008]
  2. Swiss Cancer League [KFS-3727-08-2015]
  3. Swiss National Science Foundation (SNF) [205321_176008] Funding Source: Swiss National Science Foundation (SNF)

Ask authors/readers for more resources

This study identified natural products that can inhibit oncogenic signaling in melanoma through a combination of techniques.
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 high-content 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.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available