Growth Suppression of Cancer Spheroids With Mutated KRAS by Low-toxicity Compounds from Natural Products.
Anticancer Res
; 41(8): 4061-4070, 2021 Aug.
Article
in En
| MEDLINE
| ID: mdl-34281875
ABSTRACT
BACKGROUND/AIM:
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 ANDMETHODS:
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:
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:
STAR3 is a low-toxicity compound that inhibits growth of certain tumour cells.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Biological Products
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Proto-Oncogene Proteins p21(ras)
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Spheroids, Cellular
/
Antineoplastic Agents
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Anticancer Res
Year:
2021
Document type:
Article
Affiliation country: