RT Journal Article
SR Electronic
T1 Growth Suppression of Cancer Spheroids With Mutated KRAS by Low-toxicity Compounds from Natural Products
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 4061
OP 4070
DO 10.21873/anticanres.15207
VO 41
IS 8
A1 SAYURI HASHIMOTO
A1 MASAYOSHI NAGAI
A1 KENSUKE NISHI
A1 SHUHEI ISHIKURA
A1 KAZUHIKO NAKABAYASHI
A1 RYO YAZAKI
A1 TAKASHI OHSHIMA
A1 MASAHIKO SUENAGA
A1 SENJI SHIRASAWA
A1 TOSHIYUKI TSUNODA
YR 2021
UL http://ar.iiarjournals.org/content/41/8/4061.abstract
AB 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.