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

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 (2022). High-Content Screening Pipeline for Natural Products Targeting Oncogenic Signaling in Melanoma. Journal of natural products, 85(4), pp. 1006-1017. American Chemical Society 10.1021/acs.jnatprod.1c01154

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Department of Biology > Institute of Cell Biology

UniBE Contributor:

Dobrzynski, Maciej, Mattei, Alberto, Pertz, Olivier

Subjects:

500 Science > 570 Life sciences; biology

ISSN:

0163-3864

Publisher:

American Chemical Society

Language:

English

Submitter:

Pubmed Import

Date Deposited:

03 Mar 2022 09:47

Last Modified:

05 Dec 2022 16:12

Publisher DOI:

10.1021/acs.jnatprod.1c01154

PubMed ID:

35231173

BORIS DOI:

10.48350/166325

URI:

https://boris.unibe.ch/id/eprint/166325

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