TY - JOUR
T1 - Growth suppression of cancer spheroids with mutated kras by low-toxicity compounds from natural products
AU - HASHIMOTO, SAYURI
AU - NAGAI, MASAYOSHI
AU - NISHI, KENSUKE
AU - ISHIKURA, SHUHEI
AU - NAKABAYASHI, KAZUHIKO
AU - YAZAKI, RYO
AU - OHSHIMA, TAKASHI
AU - SUENAGA, MASAHIKO
AU - SHIRASAWA, SENJI
AU - TSUNODA, TOSHIYUKI
N1 - Funding Information:
The Authors would like to thank Yuriko Isoyama and Yumiko Hirose for their technical assistance. This work was supported by Grant-in-Aid for Scientific Research (C) (KAKENHI, Grant Number 15K06847, 18K07215) from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan and the Fukuoka Foundation for Sound Health Cancer Research Fund.
Publisher Copyright:
© 2021 International Institute of Anticancer Research. All rights reserved.
PY - 2021/8
Y1 - 2021/8
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.
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.
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U2 - 10.21873/anticanres.15207
DO - 10.21873/anticanres.15207
M3 - Article
C2 - 34281875
AN - SCOPUS:85111720076
VL - 41
SP - 4061
EP - 4070
JO - Anticancer Research
JF - Anticancer Research
SN - 0250-7005
IS - 8
ER -
