TY - JOUR 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 SP - 3993 LP - 4001 DO - 10.21873/anticanres.15895 VL - 42 IS - 8 AU - KAZUMASA YOSHIDA 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 - 2022/08/01 UR - http://ar.iiarjournals.org/content/42/8/3993.abstract N2 - 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. ER -