Growth suppression of cancer spheroids with mutated kras by low-toxicity compounds from natural products

SAYURI HASHIMOTO, MASAYOSHI NAGAI, KENSUKE NISHI, SHUHEI ISHIKURA, KAZUHIKO NAKABAYASHI, RYO YAZAKI, TAKASHI OHSHIMA, MASAHIKO SUENAGA, SENJI SHIRASAWA, TOSHIYUKI TSUNODA

Research output: Contribution to journalArticlepeer-review

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 and 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: 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.

Original languageEnglish
Pages (from-to)4061-4070
Number of pages10
JournalAnticancer research
Volume41
Issue number8
DOIs
Publication statusPublished - Aug 2021

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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