Growth Suppression of Cancer Spheroids With Mutated KRAS by Low-toxicity Compounds from Natural Products.
3D floating culture
Colorectal cancer
KRAS
natural products
Journal
Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988
Informations de publication
Date de publication:
Aug 2021
Aug 2021
Historique:
received:
22
05
2021
revised:
04
06
2021
accepted:
05
06
2021
entrez:
20
7
2021
pubmed:
21
7
2021
medline:
30
7
2021
Statut:
ppublish
Résumé
Among compounds from natural products selectively suppressing the growth of cancer spheroids, which have mutant (mt) KRAS, NP910 was selected and its derivatives explored. The area of HKe3 spheroids expressing wild type (wt) KRAS (HKe3-wtKRAS) and mtKRAS (HKe3-mtKRAS) were measured in three-dimensional floating (3DF) cultures treated with 18 NP910 derivatives. The 50% cell growth inhibition (GI50) was determined by long-term 3DF (LT3DF) culture and nude mice assay. We selected NP882 (named STAR3) as the most effective inhibitor of growth of HKe3-mtKRAS spheroids with the least toxicity among NP910 derivatives. GI50s of STAR3 in LT3DF and nude mice assay were 6 μM and 30.75 mg/kg, respectively. However, growth suppression by STAR3 was observed in 50% of cell lines independent of KRAS mutation, suggesting that the target of STAR3 was not directly associated with KRAS mutation and KRAS-related signals. STAR3 is a low-toxicity compound that inhibits growth of certain tumour cells.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
Among compounds from natural products selectively suppressing the growth of cancer spheroids, which have mutant (mt) KRAS, NP910 was selected and its derivatives explored.
MATERIALS AND METHODS
METHODS
The area of HKe3 spheroids expressing wild type (wt) KRAS (HKe3-wtKRAS) and mtKRAS (HKe3-mtKRAS) were measured in three-dimensional floating (3DF) cultures treated with 18 NP910 derivatives. The 50% cell growth inhibition (GI50) was determined by long-term 3DF (LT3DF) culture and nude mice assay.
RESULTS
RESULTS
We selected NP882 (named STAR3) as the most effective inhibitor of growth of HKe3-mtKRAS spheroids with the least toxicity among NP910 derivatives. GI50s of STAR3 in LT3DF and nude mice assay were 6 μM and 30.75 mg/kg, respectively. However, growth suppression by STAR3 was observed in 50% of cell lines independent of KRAS mutation, suggesting that the target of STAR3 was not directly associated with KRAS mutation and KRAS-related signals.
CONCLUSION
CONCLUSIONS
STAR3 is a low-toxicity compound that inhibits growth of certain tumour cells.
Identifiants
pubmed: 34281875
pii: 41/8/4061
doi: 10.21873/anticanres.15207
doi:
Substances chimiques
Antineoplastic Agents
0
Biological Products
0
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4061-4070Informations de copyright
Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.