TY - JOUR T1 - Growth Suppression of Cancer Spheroids With Mutated KRAS by Low-toxicity Compounds from Natural Products JF - Anticancer Research JO - Anticancer Res SP - 4061 LP - 4070 DO - 10.21873/anticanres.15207 VL - 41 IS - 8 AU - SAYURI HASHIMOTO AU - MASAYOSHI NAGAI AU - KENSUKE NISHI AU - SHUHEI ISHIKURA AU - KAZUHIKO NAKABAYASHI AU - RYO YAZAKI AU - TAKASHI OHSHIMA AU - MASAHIKO SUENAGA AU - SENJI SHIRASAWA AU - TOSHIYUKI TSUNODA Y1 - 2021/08/01 UR - http://ar.iiarjournals.org/content/41/8/4061.abstract N2 - 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. ER -