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Growth Suppression of Cancer Spheroids With Mutated KRAS by Low-toxicity Compounds from Natural Products.

By: Sayuri Hashimoto, Masayoshi Nagai, Kensuke Nishi, Shuhei Ishikura, Kazuhiko Nakabayashi, Ryo Yazaki, Takashi Ohshima, Masahiko Suenaga, Senji Shirasawa, Toshiyuki Tsunoda

Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
2021-05-22; doi: 10.21873/anticanres.15207

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

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.