RT Journal Article
SR Electronic
T1 Cancer Spheroid Proliferation Is Suppressed by a Novel Low-toxicity Compound, Pyra-Metho-Carnil, in a Context-independent Manner
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 3993
OP 4001
DO 10.21873/anticanres.15895
VO 42
IS 8
A1 KAZUMASA YOSHIDA
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 2022
UL http://ar.iiarjournals.org/content/42/8/3993.abstract
AB Background/Aim: In a screen of compounds to selectively suppress the growth of cancer spheroids, which contained mutant (mt) KRAS, NPD10621 was discovered and associated derivatives were investigated. Materials and Methods: Spheroid areas from HCT116-derived HKe3 spheroids expressing wild type (wt) KRAS (HKe3-wtKRAS) and mtKRAS (HKe3-mtKRAS) were treated with 12 NPD10621 derivatives and measured in three-dimensional floating (3DF) cultures. Several cancers were treated with NPD1018 (pyra-metho-carnil: PMC) in 3DF cultures. In a nude mouse assay, 50% cell growth inhibition (GI50) values were determined. Results: From these 12 derivatives, PMC was the most effective inhibitor of HKe3-mtKRAS spheroid growth with the least toxicity. Furthermore, PMC-mediated growth suppression was observed in all tested cancer cell lines, independent of tissue context, driver gene mutations, and drug resistance, suggesting that the PMC target(s) was crucial for cancer growth in a context-independent manner. The GI50 value of PMC in nude mice assay was 7.7 mg/kg and nude mice that were administered 40 mg/kg PMC for 7 days did not show any abnormal blood cell count values. Conclusion: PMC is a low-toxicity compound that inhibits the growth of different tumor cell types.